Herbal compositions for the prevention or treatment of urinary incontinence and overactive bladder

ABSTRACT

Provided in one embodiment is an herbal compositions for the prevention or treatment of urogenital system disorders including urinary incontinence, overactive bladder, enuresis, benign prostatic hyperplasia, nocturia, cystitis, urinary calculi, or a urinary tract infection. Specifically one embodiment provides compositions that contain  Crateva nurvala, Equisetum arvense,  and  Lindera aggregata  and methods of use thereof.

CROSS-REFERENCE TO RELATED PATENT APPLICATIONS

This application claims the benefit of and priority to U.S. ProvisionalPatent Application 61/580,125, filed Dec. 23, 2011. All publications,patents, and patent applications cited in this Specification are herebyincorporated by reference in their entirety.

BACKGROUND

Urinary incontinence (UI) with urinary urgency and/or frequency andOveractive Bladder (OAB) are common problems affecting one in fivepeople in the United States. The total affected population is difficultto quantify as it is often under-reported. NIH and the Simon Foundationestimates suggest that between 17 and 33 million people in the UnitedStates are affected. NAFC (National Association for Continence)estimates on the basis of multiple studies and expert opinion that 25million adult Americans experience transient or chronic urinaryincontinence.

Bladder weakness affects 25% of reproductive age women, 50% ofpost-menopausal women, and 50%-75% of women in nursing homes. In men,60% over the age of 60 experience benign prostate enlargement andassociated OAB symptoms. Bladder problems remain under-diagnosed andunder-reported.

Bladder control problems can occur for many reasons. Temporary bladdercontrol problems may be caused by, for example, urinary tractinfections, vaginal infections or irritation, constipation, and certainmedicines. Longer lasting or chronic incontinence can be caused by, forexample, both overactive and weak bladder muscles, obstruction from anenlarged prostate, damage to nerves that control the bladder fromdiseases such as multiple sclerosis or Parkinson's disease, or diseasessuch as arthritis that can make walking painful and slow.

The basic types of bladder control problems include urinary urgency,urinary frequency, incontinence (bladder accidents with involuntary lossof urine) and nocturia (having to get out of bed at night for thetoilet). Overactive bladder in many cases refer to both urinaryfrequency and urgency.

There are multiple types of urinary incontinence, which include, forexample, stress incontinence, urge incontinence, overflow incontinence,and functional incontinence. Stress incontinence happens when urineleaks during exercise, coughing, sneezing, laughing, lifting heavyobjects, or other body movements that put pressure on the bladder. It isthe most common type of bladder control problem in younger andmiddle-age women. In some cases, it is related to the effects ofchildbirth. It may also begin around the time of menopause.

In some embodiments, urge incontinence can happen when a person cannothold his or her urine long enough to get to the toilet in time. Healthypeople can have urge incontinence, but it is often found in people whohave diabetes, stroke, Alzheimer's disease, Parkinson's disease, ormultiple sclerosis. It is also sometimes an early sign of bladdercancer.

In some embodiments, overflow incontinence can happen when small amountsof urine leak from a bladder that is always full. A man can have troubleemptying his bladder if an enlarged prostate is blocking the urethra.Diabetes and spinal cord injury can also cause this type ofincontinence. Functional incontinence can happen in many older peoplewho have normal bladder control. They have a hard time getting to thetoilet in time because of arthritis or other disorders that make movingquickly difficult.

Medical treatments for bladder control problems, UI, and OAB can includephysical and behavioral therapies, such as Kegel's pelvic floorexercises and bladder retraining; drug medications; devices such ascatheters; and surgery may also be an option for some sufferers. Currentdrug therapies include anticholinergics (with antispasmodic effects,e.g., oxybutinin), smooth muscle relaxants (antispasmodics), tricyclicantidepressants (e.g., imipramine), alpha-adrenergic antagonists,alpha-adrenergic agonists (e.g., phenylpropanolamine), prostaglandinsynthesis inhibitors, calcium channel blockers and others (Sullivan andAbrams, Eur. Urol., 36 Suppl 1:89-95 (1999); Andersson, Baillieres BestPract. Res. Clin. Obstet. Gynaecol., 14(2): 291-313 (2000); Owens andKarram, Drug Saf., 19(2): 123-39 (1998); Wada et al., Arch. Int.Pharmacodyn Ther., 330(1): 76-89 (1995)). Unfortunately, most drugtreatments are associated with unpleasant side effects, and this affectson patient compliance (Sullivan and Abrams, Eur. Urol., 36 Suppl 1:89-95 (1999); Andersson, Baillieres Best Pract. Res. Clin. Obstet.Gynaecol., 14(2): 291-313 (2000); Owens and Karram, Drug Saf.,19(2):123-39 (1998); Wada et al., Arch. Int. Pharmacodyn Ther., 330(1):76-89 (1995))2-5.

Acetylcholine is the primary excitatory neurotransmitter involved inbladder emptying. Certain drugs commonly prescribed for urinaryincontinence, such as oxybutynin hydrochloride, inhibit the muscarinicaction of acetylcholine on smooth muscle, producing a directantispasmodic action. These drugs relax the detrusor muscle. Wada Y. etal., Arch. Int. Pharmacodyn. Ther., 330(1):76-89 (1995); Tapp A. J. S.et al., Brit. J. Obstetrics Gynecology, 97: 521-6 (1990). Thesemedications also produce unwanted anticholinergic effects, such as drymouth, blurred vision and constipation. Pathak A S, Aboseif S R.Overactive Bladder: Drug therapy versus nerve stimulation. Nat ClinPract Urol, 2(7): 310-311, 2005; Wein (2001). Natural therapies havealso been investigated for this condition (Steels et al., Aust.Continence J., 7(2): 34-37 (2001); Karantanis et al., Aust. ContinenceJ., 6(4): 6-7 (2000); Arya et al., Obstetrics and Gynecology, 96(1):85-89 (2000); Bryant et al., Aust. Continence J., 6(4): 8 (2000)). InAyurveda, Crateva nurvala is a drug highly regarded for its use in themanagement of uropathies (Nadkarni, Indian Materia Medica. BombayPopular Prakashan). Western traditional treatments recommend the use ofEquisetum arvense (British Herbal Pharmacopeia. Publ: British HerbalMedicine Association 1983). Chinese medicine values Lindera for itsvarious properties (Bensky D and Gamble A, 1993. Chinese Herbal MateriaMedica, Revised Edition. England Press, Seattle, Wash., USA.)

Isolated clinical studies conducted using herb-based natural therapiesfor urinary incontinence include Crateva nurvala herb, acupuncture anddietary intervention such as modification of dietary intake. Deshpandeet al., Indian J. Med. Res. 76(supp): 46-53, 1982; Karantanis et al.,Aust. Continence J., 6(4): 6-7, 2000; Arya et al., Obstetrics andGynecology, 96(1): 87-89, 2000; Bryant et al., Aust. Continence J.,6(4): 8, 2000.

In some embodiments, overactive bladder (OAB) is a condition that can becharacterized by the sudden need to urinate. If that need results in theunintentional leakage of urine, the condition is called urgeincontinence (“OAB wet”). Thus, urge incontinence falls within thegeneral definition of OAB in some embodiments. In some embodiments, OABcan result from the sudden, involuntary contraction of the muscle in thewall of the urinary bladder. Approximately one-third of people with OABalso experience urge incontinence (“OAB wet”), while approximatelytwo-thirds have OAB without urge incontinence (“OAB dry”). According tothe National Overactive Bladder Evaluation, OAB affects 16.5% of thepopulation, with 16.9% of women and 16.0% of men affected. Stewart etal., World J. Urol. 20: 327-336, (2003). OAB, like urinary incontinence,is treated primarily with anticholinergic drugs (e.g., oxybutinin).These inhibit the neurotransmitter acetylcholine from attaching to thebladder muscle, and thereby reduce the frequency and intensity ofcontractions of the bladder. Unfortunately, adverse side effects ofthese drugs include dry mouth, dry eyes, constipation, and headache.Anderson, Urology, 3A: 32-41 (2004); Cruz, Urology. 3A: 65-73 (2004);Appell et al., Mayo Clinical Proc., 78:696-702. (2003).

There are currently no medications that specifically target incontinenceor OAB symptoms without having side effects elsewhere in the body.Herbal approaches to bladder problems that improve the tone and tissuestrength of the bladder and surrounding area are proving to be effectivefor bladder control problems. (See, U.S. Pat. No. 7,378,115; and SchaussA G, Spiller G, Chaves S, Gawlicka A, 2006. Reducing the symptoms ofoveractive bladder and urinary incontinence: results of a two-month,double-blind, placebo-controlled clinical trial. Poster presentationFASEB, San Francisco, April, 2006.) The timeframe for these herbalpreparations to produce effective improvements in bladder control is twoto three months. In may instances, the length of time before effectiveresults are experienced can result in distress and discomfort for thepatient, as well as an expected reduction in patient compliance with thetreatment. Herbal treatments that produce results within a shortertimeframe are warranted.

Thus, a need exists for the identification of new herb-containingcompositions that can provide effective prevention or treatment ofurinary incontinence and overactive bladder.

SUMMARY

One embodiment described herein is related to herbal compositions usefulfor the prevention or treatment of urinary incontinence and overactivebladder. The herb-containing compositions provide herein can beformulated in a dry delivery system, liquid delivery system, or acontrolled-release vehicle. In one embodiment, the herb-containingcompositions are formulated as oral dosage units which include a tablet;dry powder; capsule; and caplet.

One embodiment provides an herb-containing composition, comprising (i) aCrateva nurvala extract preparation; (ii) an Equisetum arvense extractpreparation; and (iii) a Lindera aggregata extract preparation; whereinthe herb-containing composition is formulated as an oral dosage unit.

An alternative embodiment provides an herb-containing composition,comprising: (i) a Crateva nurvala stem/bark extract preparation present;(ii) an Equisetum arvense stem extract preparation; (iii) a Linderaaggregata root extract preparation; wherein the herb-containingcomposition is formulated as an oral dosage unit, and wherein theEquisetum arvense stem extract preparation and the Lindera aggregataroot extract preparation are present at the same concentration.

An effective daily amount of each herb ranges from about 1 g to 18 gCrateva nurvala, about 750 mg to 12 g Equisetum arvense and about 750 mgto 12 g Lindera aggregata. In an alternative embodiment, an effectivedaily amount of each herb ranges from about 3 g to 12 g Crateva nurvala,about 1.5 g to 6 g Equisetum arvense and about 1.5 g to 6 g Linderaaggregata. In another alternative embodiment, an effective daily amountof each herb ranges from about 4 g to 8 g Crateva nurvala, about 2 g to4 g Equisetum arvense and about 2 g to 4 g Lindera aggregata. In anotheralternative embodiment, an effective daily amount of each herb containsabout 6 g Crateva nurvala, about 3 g Equisetum arvense and about 3 gLindera aggregata.

In an alternative embodiment, the effective daily amount is taken in twoequivalent doses. For example, in one embodiment, each doses containsabout 3 g Crateva nurvala, about 1.5 g Equisetum arvense and about 1.5 gLindera aggregata.

In another alternative embodiment, the effective daily amount is takenin three equivalent doses. For example, in one embodiment, each dosescontains about 2 g Crateva nurvala, about 1 g Equisetum arvense andabout 1 g Lindera aggregata.

An alternative embodiment provides an herb-containing composition withat least one of the herbal components is a standardized preparation. Inan alternative embodiment, the herb-containing composition has two ofthe herbal components as standardized preparations. In anotherembodiment, all three herbal components of the herb-containingcomposition (Crateva nurvala, Equisetum arvense and Lindera aggregata)are standardized preparations.

An alternative embodiment provides a kit for the prevention or treatmentof the symptoms of urinary incontinence or overactive bladder comprisingCrateva nurvala, Equisetum arvense and Lindera aggregata, eachseparately in the form of a tablet. In an alternative embodiment, two orthree herbs are combined in a single tablet. In an alternativeembodiment, the kit comprises sufficient tablets for the prevention ortreatment of the symptoms of urinary incontinence or overactive bladderin a subject for 30 days. In alternative embodiments, the kit comprisessufficient tablets for the prevention or treatment of the symptoms ofurinary incontinence or overactive bladder in a subject for 7, 14, 21,or 28 days. In another alternative embodiments, the kit comprises asufficient number of tablets for the prevention or treatment of thesymptoms of urinary incontinence or overactive bladder in a subject for2, 3, 4, 5, 6, 9, or 12 months.

Another embodiment provides a method for the prevention or treatment ofthe symptoms of urinary incontinence or overactive bladder. The methodcomprises administering an herb-containing composition to a subject inneed thereof, the herb-containing composition comprising: (i) a Cratevanurvala stem/bark extract preparation; (ii) an Equisetum arvense stemextract preparation; and (iii) a Lindera aggregata root extractpreparation; wherein the herb-containing composition is formulated as anoral dosage unit.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be more fully understood by reference to thefollowing drawings, which are for illustrative purposes only:

FIG. 1 is a histogram graph showing the percentage (%) of participantpopulation affected by symptoms of urinary incontinence and overactivebladder during clinical assessment in one embodiment.

FIG. 2 is a histogram graph showing the percentage (%) of participantpopulation experiencing symptoms of urinary incontinence and overactivebladder during clinical assessment in one embodiment.

FIG. 3 is a histogram graph showing UDI Average Bothered Rating forsymptoms during clinical assessment in one embodiment.

FIG. 4 is a histogram graph showing the percentage (%) of participantpopulation experiencing symptoms IIQ during clinical assessment in oneembodiment.

FIG. 5 is a histogram graph showing percentage (%) reduction in UDIratings during clinical assessment in one embodiment.

DETAILED DESCRIPTION

It is to be appreciated therefore that certain aspects, modes,embodiments, variations and features of the invention described below invarious levels of detail in order to provide a substantial understandingof the present invention. In general, such disclosure providesbeneficial herb-containing compositions, combinations of suchcompositions with other dietary supplement compositions, and relatedmethods of producing and using same.

Accordingly, the various aspects of the present invention relate totherapeutic or prophylactic uses of certain particular herb-basedcompositions in order to prevent or treat a disease, injury or conditionrelated to urinary incontinence. Accordingly, various particularembodiments that illustrate these aspects follow.

It is to be appreciated that the various modes of treatment orprevention of medical conditions as described are intended to mean“substantial”, which includes total but also less than total treatmentor prevention, and wherein some biologically or medically relevantresult is achieved.

A “subject” as described in some embodiments herein can be a mammal,such as a human, but can also be an animal, such as domestic animals(e.g., dogs, cats and the like), farm animals (e.g., cows, sheep, pigs,horses and the like), and laboratory animals (e.g., rats, mice, guineapigs and the like).

An “effective amount” of a composition as described in some embodimentsherein can be a quantity sufficient to achieve a desired therapeuticand/or prophylactic effect, for example, an amount which results in theprevention of, or a decrease in the symptoms associated with, a diseasethat is being treated. The amount of composition administered to thesubject, particularly one in need of the composition, can depend on thetype and severity of the disease and on the characteristics of theindividual, such as general health, age, sex, body weight and toleranceto drugs. It can also depend on the degree, severity and type ofdisease. A skilled artisan will be able to determine appropriate dosagesdepending on these and other factors. Typically, an effective amount ofthe compositions described herein can be sufficient for achieving atherapeutic or prophylactic effect.

In some embodiments, it can be advantageous to formulate oralcompositions in dosage unit form for ease of administration anduniformity of dosage. Dosage unit forms described in some embodimentscan refer to physically discrete units suited as unitary dosages for thesubject to be treated; each unit containing a predetermined quantity ofactive composition calculated to produce the desired therapeutic effectin association with the suitable pharmaceutical carrier. Thespecification for the dosage unit forms provided in one embodiment maybe dictated by and directly dependent on the characteristics of thedietary supplement and the particular therapeutic effect to be achieved,and the limitations inherent in the art of producing such an activecomposition for the treatment of individuals. The pharmaceuticalcompositions can be included in a container, pack, or dispenser,together with instructions for administration. Generally, in someembodiments an oral dose is taken two-times to four-times daily, untilsymptom relief is apparent. The compositions provided herein can also beadministered in combination with each other, or with one or moreadditional therapeutic compositions.

Herbal Ingredients

Crateva nurvala (or “C. nurvala”) is a moderate-sized tree attaining aheight of over 15 meters; it is named after cratevas (Krateuas), a Greeknaturalist and physician of the first Century B.C. Common throughoutIndia, the much-branched tree with a head of glossy trifoliate leaveslooks very majestic when in full bloom from March to May (earlier in theSouth). The bark of the tree is reported to be used as a demulcent,antipyretic, sedative, alterative and tonic.

Equisetum arvense (or “E. arvense”) (botanical synonyms and common namesinclude, for example, Horsetail; Shave-grass; Bottle-brush;Paddock-pipes; Dutch Rushes; Pewterwort; Shavegrass; Pewterwort;Bottlebrush; Horsetail rush; Paddock-pipes; Dutch rushes; Mare's tail)is a European herb that grows in moist waste places throughout temperateregions of the world and is cultivated in Yugoslavia. This perennialplant is common to moist loamy or sandy soil all over North America andEurasia. Compared to the other herbs in the plant kingdom, horsetail isvery rich in silicon. Equisetum is used medicinally. The sterile stemsare harvested in summer and dried. The barren stems are useful asmedicine, appearing after the fruiting stems have died down, and areused in their entirety, cut off just above the root. The herb is usedeither fresh or dried, but can be most efficacious when fresh in oneembodiment. A fluid extract is prepared from it. The ashes of the plantare also employed.

Lindera aggregata (or “L. aggregata”) (botanical synonyms and commonnames include Lindera strychnifolia, Japanese evergreen spicebush,Chinese allspice, Evergreen Lindera, Kosterm, Uyaku (Japanese), Oyak(Korean)) is a Chinese herb grown in locations including Zhejiang,Hunan, Anhui, Guangdong, and Guangxi. (Bensky and Gamble). Lindera is anevergreen Shrub growing to 9 m (29 ft 6 in). The flowers are dioecious(i.e., individual flowers are either male or female, but only one sex isto be found on any one plant so both male and female plants must begrown if seed is needed). The plant is not self-fertile. The plant tendsto prefer light (sandy), medium (loamy) and heavy (clay) soils,preferring moist soil. The plant tends to prefer acid and neutral soilsand can grow in very acid soils and in semi-shade (light woodland). Itcan be harvested in winter or spring (Bensky and Gamble). The root andleaves are used therapeutically.

Herbs are useful in various forms, for example, as a homogenized mixtureobtained by grinding or chopping a herb. The herbs are optionallysubjected to processing such as extractions, for example by obtaining afiltrate by filtering or a supernatant by centrifugation. Known methodsare readily used to extract a leaf, root, seed, stem, bark etc asappropriate. In certain embodiments, extracts that contain purifiedactive ingredients are prepared. An isolated active ingredient is aningredient purified from C. nurvala, E. arvense and L. aggregata thathas activity to control (i.e., typically reduce) the symptoms UI/OAB ina subject. Administration or use of an isolated active ingredient ofanother herb of the compositions herein, is considered to be a use oradministration of the herb itself. The inventor has identified certaincompounds in the herbs above without wishing to be bound by theory aboutcompounds and metabolites in the herbs and mechanisms of how the herbsin the compositions herein control the symptoms UI/OAB.

In one embodiment, the C. nurvala herb preparation can be extracted fromthe stem and/or bark of the plant, and the preparation is present at aconcentration at least about 3,000 mg dry weight equivalents per oraldosage unit. That is, the starting material is 3,000 mg of C. nurvaladry stem/bark. This starting material is eventually concentrated duringthe manufacturing process to a ratio (“extract ratio”) of at least about5 (i.e., 5:1), such as at least about 10, such as at least about 20,such as at least about 25, such as at least about 30, such as at leastabout 35, such as at least about 40. In one embodiment, the ratio isbetween about 25 and about 35. As an illustrative example, a ratio of 10would be equivalent to 300 mg of C. nurvala preparation. Accordingly,300 mg of C. nurvala stem/bark preparation (which is concentrated) isequivalent to 3,000 mg dry weight of C. nurvala stem/bark or 3,000 mg ofC. nurvala dry stem/bark starting material. In one embodiment, the C.nurvala herb preparation is derived from the stem and/or bark parts ofthe C. nurvala herb, i.e., a C. nurvala stem/bark extract preparation.

The E. arvense herb preparation can be extracted from the stem of theplant, and the preparation is present at a concentration of at leastabout 1,500 mg dry weight equivalents per oral dosage unit. That is, thestarting material is 1,500 mg of E. arvense herb. This starting materialis eventually concentrated during the manufacturing process to anextract ratio of at least about 5, such as at least about 8, such as atleast about 10, such as at least about 15. As an illustrative example, aratio of 4 or 5 would be equivalent to 375 mg or 300 mg, respectively,of E. arvense herb preparation. Thus, in the case of a concentrationratio of 5, for example, 300 mg of E. arvense herb preparation (which isconcentrated) is equivalent to 1,500 mg dry weight of E. arvense herb or1,500 mg of E. arvense dry herb starting material. In one embodiment,the E. arvense herb preparation is derived from the stem parts of the E.arvense herb, i.e., a E. arvense stem extract preparation.

The L. aggregata herb preparation can be extracted from the stem of theplant, and the preparation is present at a concentration of at leastabout 1,500 mg dry weight equivalents per oral dosage unit. That is, thestarting material is 1,500 mg of L. aggregata herb. This startingmaterial is eventually concentrated during the manufacturing process toan extract ratio of at least about 5, such as at least about 8, such asat least about 10, such as at least about 15. As an illustrativeexample, a ratio of 4 or 5 would be equivalent to 375 mg or 300 mg,respectively, of L. aggregata herb preparation. Thus, in the case of aconcentration ratio of 5, for example, 300 mg of L. aggregata herbpreparation (which is concentrated) is equivalent to 1,500 mg dry weightof L. aggregata herb or 1,500 mg of L. aggregata dry herb startingmaterial. In one embodiment, the L. aggregata herb preparation isderived from the root parts of the L. aggregata herb, i.e., a L.aggregata root extract preparation.

In some embodiments, the herbal ingredients described herein, alone orin combination, can provide the following remedy or support:

Bladder Support

Crateva nurvala, an Ayurvedic herb, has been used for many centuries forurinary support and to help with diseases of the bladder.¹ It has toniceffects on the bladder and is recommended for poor bladder tone andsymptoms of incontinence.

Kidney/Bladder Stones

Crateva and Horsetail balance urinary minerals and reduce the likelihoodof stone formation.^(2, 3) A key constituent of Crateva, lupeol, hasbeen shown in a number of studies to have anti-oxaluric andanti-calcuric effects leading to increased spontaneous passing of thesetwo most common forms of stones as well as symptomatic relief.^(2, 4, 5)Horsetail constituents inhibit xanthine oxidase and subsequent uratecalculi formation.⁷ It is thought that this effect is promoted by atonic contractile effect of Crateva and Horsetail on the smooth muscle,which also assists with bladder control.^(1, 2, 4)

Incontinence/OAB

Crateva and Horsetail help to improve the tone of the bladder wall.Crateva has beneficial effects on neurogenic bladder andpost-prostatectomic atony of the bladder.¹ Crateva is shown to produce asignificant reduction in urinary symptoms of frequency, incontinence,pain and retention of urine in men with hypotonic bladder as a result ofbenign prostatic hypertrophy. Crateva acts to increase the tone of thebladder and the expulsive force of urine, thereby helping effectiveevacuation.¹ Crateva normalizes the tone of the urinary bladder andsignificantly decreases residual urine volume.

Animal studies support this. Crateva has been shown to increase the toneof both smooth and skeletal muscle in vitro.⁶ Forty days of treatmentproduced dramatic improvement.

Research also supports the effectiveness of the combined Crateva andHorsetail for bladder control.^(8, 9) This combination showedimprovements in bladder emptying frequency, leakage, urgency and bladderpain or discomfort with best results occurring after two to three monthsof treatment.^(8,9)

Lindera has a long history of use in Traditional Chinese Medicine forkidney and bladder health and is specific for frequent urination andloss of bladder control.^(21,22) Lindera is also recommended for thetreatment of renal disease.²¹

Quality of Life

Poor bladder control is shown to negatively affect emotional health andto reduce quality of life for the sufferer.^(10,11) Research has shownthe Crateva and Horsetail combined significantly improved quality oflife measurements including feeling less frustration, increased socialactivities, and better travel.^(8, 9)

Anti-Inflammatory

All of three herbs described herein show anti-inflammatory effects.¹²⁻¹⁸Crateva and Lindera have anti-inflammatory and antibacterialproperties.¹²⁻¹⁸ The positive effect on chronic urinary tract infectionsis most likely a combination of anti-bacterial and anti-inflammatoryactions.

Kidney Protective

Crateva and Lindera are also shown to have kidney protective effects;Crateva has been shown to be nephroprotective in rats exposed to toxicdoses of cadmium, while Lindera preserves renal function in animals withdiabetic nephropathy.^(19,20)

Animal research demonstrates that Lindera slows the progression ofdiabetic nephropathy (destruction of the kidneys that can occur as acomplication of diabetes) and could therefore be used as a preventativeapproach to protect renal function from deterioration.²⁰ Use of Linderacan result in improved renal function, as evaluated by creatinineclearance and serum creatinine. Kidneys of the Lindera treated groupshowed glomeruli with greater area and cell population.

Anti-Oxidant/Anti-Aging

More recent research has shown that Lindera has potent antioxidanteffects to preserve tissue and function of urinary system. It has potentantioxidant scavenging activity against ROS and RNS (reactive oxygenspecies and reactive nitrogen species—both common oxidants that damagebody tissues) that effectively inhibits lipid peroxidation.²³ Linderaextracts show protection against neuronal oxidative injury and may be ofbenefit to protect against neuronal Central nervous systemdegeneration.²⁴ Lindera also has antibacterial effects.²¹

Joint Support

Lindera is also used traditionally for rheumatic complaints, andmultiple studies have shown that Lindera or Lindera extracts reduceinflammation.¹⁵⁻¹⁷ Alkaloids derived from Lindera have been shown inanimal studies to have anti-inflammatory effects and to be of benefitfor rheumatoid arthritis (RA).¹⁵ Lindera has also been shown to inhibitthe effects of inflammatory mediators from macrophages. These helpillustrate therapeutic efficiency on the inflammation and jointdestruction in RA.¹⁶ This supports the use of Lindera for analgesic andanti-inflammatory actions to improve symptoms of RA and protect jointsfrom destruction.¹⁷

Cardiovascular Support

Lindera is traditionally recommended for the treatment of cardiacsupport. Animal studies have shown that Lindera can improve heartfunction.²²

Herb-Containing Compositions

One embodiment described herein provides herb-containing compositionsuseful in a method of prophylaxis or treatment of disorders of theurogenital system—e.g., urinary incontinence, enuresis (e.g.,bed-wetting), benign prostatic hyperplasia, overactive bladder,nocturia, urinary calculi, cystitis, and urinary tract infection (or“UTI”). In particular, one embodiment provides a composition, whichcontains C. nurvala, E. arvense, and L. aggregata; in one embodiment thecomposition is useful in the prevention and treatment of disorders ofthe urogenital system. In one embodiment, the herb-containingcomposition contains C. nurvala extract preparation, E. arvense extractpreparation, and L. aggregata preparation.

In one embodiment, the herb-containing composition is an oral supplementincluded in a dry delivery system, e.g., tablet, dry powder, and drymeal replacement mixture. In another embodiment, the herb-containingcomposition is an oral supplement included in a liquid delivery system,e.g., capsule, caplet, or beverage. In another embodiment, theherb-containing composition is an oral supplement included in acontrolled-release vehicle, e.g., tablet, caplet, and capsule.

In one embodiment, the herb-containing composition contains from about1,000 mg to about 6,000 mg dry weight equivalents C. nurvala stem/barkextract per oral dosage unit. In another embodiment, the herb-containingcomposition contains from about 1,000 mg to about 4,000 mg dry weightequivalents C. nurvala stem/bark extract per oral dosage unit. Inanother embodiment, the herb-containing composition contains from about2,500 mg to about 3,500 mg dry weight equivalents C. nurvala stem/barkextract per oral dosage unit. In one embodiment, the herb-containingcomposition contains about 3,000 mg dry weight equivalents C. nurvalastem/bark extract per oral dosage unit. A C. nurvala stem/bark extractis an extract prepared using both the stem parts and bark of the C.nurvala herb.

In another embodiment, the herb-containing composition contains fromabout 1,000 mg to about 6,000 mg dry weight equivalents C. nurvala stemextract per oral dosage unit. In another embodiment, the herb-containingcomposition contains from about 1,000 mg to about 4,000 mg dry weightequivalents C. nurvala stem extract per oral dosage unit. In anotherembodiment, the herb-containing composition contains from about 2,500 mgto about 3,500 mg dry weight equivalents C. nurvala stem extract peroral dosage unit. In one embodiment, the herb-containing compositioncontains about 3,000 mg dry weight equivalents C. nurvala stem extractper oral dosage unit.

In another embodiment, the herb-containing composition contains fromabout 1,000 mg to about 6,000 mg dry weight equivalents C. nurvala barkextract per oral dosage unit. In another embodiment, the herb-containingcomposition contains from about 1,000 mg to about 4,000 mg dry weightequivalents C. nurvala bark extract per oral dosage unit. In oneembodiment, the herb-containing composition contains from about 2,500 mgto about 3,500 mg dry weight equivalents C. nurvala bark extract peroral dosage unit. In one embodiment, the herb-containing compositioncontains about 3,000 mg dry weight equivalents C. nurvala bark extractper oral dosage unit.

In one embodiment, to prepare the herb-containing composition, the barkand/or stems of C. nurvala are isolated from the rest the C. nurvalaplant and dried. The dried bark and stems of C. nurvala are extractedusing 70% ethanol/water. The liquid extract is then concentrated to aratio of 10:1. Maltodextrin is used as an excipient. The final product,i.e., C. nurvala stem/bark extract, used in the herb-containingcomposition is a brown to dark brown powder. In an alternativeembodiment, the liquid extract is then concentrated to a ratio ofbetween about 25 and 35. Maltodextrin is used as an excipient.

In one embodiment, the E. arvense herb preparation component of theherb-containing composition is derived from the leaf of the E. arvenseherb. In one embodiment, the E. arvense herb preparation component ofthe herb-containing composition is derived from the stem of the E.arvense herb. In another embodiment, the E. arvense herb preparationcomponent of the herb-containing composition is derived from a mixtureof plant parts of the E. arvense herb. In another embodiment, the E.arvense herb preparation component of the herb-containing composition isderived from all the parts of the plant that extend above-ground. In oneembodiment, the herb-containing composition contains from about 1 mg toabout 3,000 mg dry weight equivalents E. arvense herb preparation peroral dosage unit. In another embodiment, the herb-containing compositioncontains from about 500 mg to about 2,500 mg dry weight equivalents E.arvense herb preparation per oral dosage unit. In another embodiment,the herb-containing composition contains from about 1,000 mg to about2,000 mg dry weight equivalents E. arvense herb preparation per oraldosage unit. In another embodiment, the herb-containing compositioncontains from about 1,300 mg to about 1,600 mg dry weight equivalents E.arvense herb preparation per oral dosage unit. In one embodiment, theherb-containing composition contains about 1,500 mg dry weightequivalents E. arvense stem extract per oral dosage unit.

In one embodiment, the L. aggregata herb preparation component of theherb-containing composition is derived from the roots of the L.aggregata herb. In one embodiment, the L. aggregata herb preparationcomponent of the herb-containing composition is derived from the leafand/or stem of the L. aggregata herb. In another embodiment, the L.aggregata herb preparation component of the herb-containing compositionis derived from a mixture of plant parts of the L. aggregata herb. Inanother embodiment, the L. aggregata herb preparation component of theherb-containing composition is derived from all the parts of the plantthat extend above-ground and/or below-ground. In one embodiment, theherb-containing composition contains from about 1 mg to about 3,000 mgdry weight equivalents L. aggregata herb preparation per oral dosageunit. In another embodiment, the herb-containing composition containsfrom about 500 mg to about 2,500 mg dry weight equivalents L. aggregataherb preparation per oral dosage unit. In another embodiment, theherb-containing composition contains from about 1,000 mg to about 2,000mg dry weight equivalents L. aggregata herb preparation per oral dosageunit. In another embodiment, the herb-containing composition containsfrom about 1,300 mg to about 1,600 mg dry weight equivalents L.aggregata herb preparation per oral dosage unit. In some embodiments,the L. aggregata herb preparation can be present at a comparable, suchas the same, concentration as the E. arvense preparation. In oneembodiment, the herb-containing composition contains about 1,500 mg dryweight equivalents L. aggregata root extract per oral dosage unit.

In some instances, silicon is identified as a contributor to thebiological activity of E. arvense herb. Non-standardized preparations ofE. arvense herb generally contain silicon from about 1.2% to about 6.9%silicon based on total dry weight of preparation. In one embodiment, ithas been determined that batch variation in the silicon content of E.arvense herb preparations can have negative effects on the biologicalactivity of the composition described herein. This problem can beresolved in one embodiment by providing an E. arvense herb preparationwith optimized, standardized silicon content. Accordingly, in oneembodiment, the silicon content of the E. arvense herb preparation inthe herb-containing preparation can be standardized. The use of astandardized preparation E. arvense herb can be advantageous because theinter-batch variation of silicon can be reduced, thus the compositiondescribed herein can yield more consistent preventative or therapeuticeffect. In one embodiment, the E. arvense herb preparation isstandardized to contain from about 3% silicon to about 13% silicon basedon the total dry weight of the E. arvense herb preparation. In anotherembodiment, the E. arvense herb preparation is standardized to containfrom about 5% silicon to about 10% silicon based on the total dry weightof the E. arvense herb preparation. In another embodiment, the E.arvense herb preparation is standardized to contain at least about 6%silicon based on the total dry weight of the E. arvense herbpreparation.

In addition to silicon, E. arvense contains about 5 percent of asaponin, designated equisetonin, and several flavone glycosides (i.e.,flavonoids) including isoquercetrin, galuteolin, and equisetrin.Isoquercetrin (i.e., isoquercitrin; Quercetin 3-O-β-D-glucopyranoside;4H-1-Benzopyran-4-one,2-(3,4-dihydroxy-phenyl)-3-(β-D-glucofuranosyloxy)-5,7-dihydroxy-).Flavonoids, e.g., isoquercetrin, may have important pharmacologicalproperties. Many flavonoids are diuretic, some are antispasmodic,anti-inflammatory, antiseptic and even antitumor. However, thepredominant action of the flavonoids as a group is on the vascularsystem. The flavone glycosides and the saponin likely combine to accountfor the diuretic action of E. arvense.

One embodiment provides an herb-containing composition, comprising: a C.nurvala stem/bark preparation present at a concentration at least about3,000 mg dry weight equivalents per oral dosage unit; an E. arvense stemextract preparation at a concentration of at least about 1,500 mg dryweight equivalents per oral dosage unit; and a L. aggregata root extractpreparation at a concentration of at least about 1,500 mg dry weightequivalents per oral dosage unit. Optionally, the composition canfurther comprise a total silicon concentration of at least about 32.5 mgdry weight equivalents per oral dosage unit; a phosphorus concentrationof at least about 24.9 mg dry weight equivalents per oral dosage unit; amagnesium concentration of at least about 14.5 mg dry weight equivalentsper oral dosage unit; and a calcium concentration of at least about 16.3mg dry weight equivalents per oral dosage unit.

Another embodiment provides an herb-containing composition, comprising aC. nurvala stem/bark preparation, an E. arvense stem extract preparationwith a total flavonoid content from about 0.01% to about 3% totalflavonoids based on the total dry weight of the E. arvense preparation,and a L. aggregata root extract preparation; wherein the total flavonoidcontent is expressed as isoquercetrin and wherein the herb-containingcomposition is formulated as an oral dosage unit. In one embodiment, theE. arvense herb preparation can be a standardized E. arvense stemextract preparation. In one embodiment, the standardized E. arvense herbpreparation further comprises a total flavonoid content from about 0.1%to about 2.5% total flavonoids based on the total dry weight of the E.arvense preparation and expressed as isoquercetrin. In one embodiment,the standardized E. arvense herb preparation comprises a total flavonoidcontent from about 0.5% to about 1.5% total flavonoids based on thetotal dry weight of the E. arvense preparation, wherein the totalflavonoid content is expressed as isoquercetrin. In one embodiment, thestandardized E. arvense herb preparation comprises a total flavonoidcontent from at least about 0.8% total flavonoids based on the total dryweight of the E. arvense preparation, wherein the total flavonoidcontent is expressed as isoquercetrin.

Other embodiments of the herbal composition are presented in Table 1.

TABLE 1 Ranges of effective daily amounts of the herbal compositionComponent Range A (g/day) Range B (g/day) Range C (g/day) C. nurvala  1-18   3-12 4-8 E. arvense 0.75-12 1.5-6 2-4 L. aggregata 0.75-121.5-6 2-4

An alternative embodiment provides an herb-containing composition withat least one of the herbal components is a standardized preparation. Inan alternative embodiment, the herb-containing composition has two ofthe herbal components as standardized preparations. In anotherembodiment, all three herbal components of the herb-containingcomposition (Crateva nurvala, Equisetum arvense and Lindera aggregata)are standardized preparations. Various embodiments of the standardizedpreparations are provided in Table 2. For example, in alternativeembodiment A, all three herbs are non-standardized, while in embodimentG, all three herbs are standardized.

TABLE 2 Various embodiments of the standardized preparations of theherbal composition Emodiment C. nurvala E. arvense L. aggregata A — — —B * — — C — * — D — — * E * * — F — * * G * * * NOTE: Herbs denoted withan asterisk (*) are standardized; herbs denoted with a dash (—) arenon-standardized.

One embodiment provides a pharmaceutical composition comprising theherb-containing composition and a pharmaceutically-acceptable carrier.

Standardization

In some embodiments, it has been determined that batch variation in thesilicon content and/or flavonoid content expressed as isoquercetrin ofE. arvense herb preparations can have negative effects on the biologicalactivity of the composition described herein. This problem has beenresolved in some embodiments by providing E. arvense herb preparationswith optimized, standardized silicon content and/or flavonoid contentexpressed as isoquercetrin. One embodiment provides an herb-containingcomposition, comprising a C. nurvala preparation, a L. aggregatapreparation, and a standardized E. arvense herb preparation with asilicon content from about 3% to about 13% silicon based on total dryweight of the E. arvense preparation, wherein the herb-containingcomposition is formulated as an oral dosage unit. Accordingly, for 1,500mg dry weight of E. arvense herb or 1,500 mg of E. arvense dry herbstarting material, which produces 300 mg of E. arvense herb preparation(which is concentrated), a silicon content from about 3% to about 13%would represent approximately 9 to 39 mg silicon.

In one embodiment, the standardized E. arvense herb preparation furthercomprises a total flavonoid content from about 0.01% to about 3% totalflavonoids based on the total dry weight of the E. arvense preparation,wherein the total flavonoid content is expressed as isoquercetrin. Inone embodiment, the standardized E. arvense herb preparation furthercomprises a total flavonoid content from about 0.1% to about 2.5% totalflavonoids based on the total dry weight of the E. arvense preparationand expressed as isoquercetrin. In one embodiment, the standardized E.arvense herb preparation further comprises a total flavonoid contentfrom about 0.5% to about 1.5% total flavonoids based on the total dryweight of the E. arvense preparation, wherein the total flavonoidcontent is expressed as isoquercetrin. In one embodiment, thestandardized E. arvense herb preparation further comprises a totalflavonoid content from at least about 0.8% total flavonoids based on thetotal dry weight of the E. arvense preparation, wherein the totalflavonoid content is expressed as isoquercetrin.

In another embodiment, it has been determined that batch variation inthe total flavonoid content (expressed as isoquercetrin content) of E.arvense herb preparations can have negative effects on the biologicalactivity of the composition described herein. This problem has beenresolved in some embodiments by providing an E. arvense herb preparationwith optimized, standardized total flavonoid content (expressed asisoquercetrin content). Accordingly, in one embodiment, the totalflavonoid content (expressed as isoquercetrin content) of the E. arvenseherb preparation in the herb-containing preparation is standardized. Theuse of a standardized preparation E. arvense herb is advantageousbecause the inter-batch variation of total flavonoid content (expressedas isoquercetrin content) is reduced, thus the composition providedherein can yield more consistent preventative or therapeutic effect. Inone embodiment, the E. arvense herb preparation is standardized tocontain from about 0.01% flavonoids to about 3% flavonoids based on thetotal dry weight of the E. arvense herb preparation, wherein the totalflavonoids are expressed as isoquercetrin equivalents. In anotherembodiment, the E. arvense herb preparation is standardized to containfrom about 0.1% flavonoids to about 2.5% flavonoids based on the totaldry weight of the E. arvense herb preparation, wherein the totalflavonoids are expressed as isoquercetrin equivalents. In anotherembodiment, the E. arvense herb preparation is standardized to containfrom about 0.5% flavonoids to about 1.5% flavonoids based on the totaldry weight of the E. arvense herb preparation, wherein the totalflavonoids are expressed as isoquercetrin equivalents. In anotherembodiment, the E. arvense herb preparation is standardized to containat least about 0.8% flavonoids based on the total dry weight of the E.arvense herb preparation, wherein the total flavonoids are expressed asisoquercetrin equivalents.

In one embodiment, the E. arvense herb preparation is standardized toorganic silicon content by a solvent extraction process using rawmaterial with a silicon content that met a minimum silicon content,e.g., 3% silicon. In one embodiment, the E. arvense herb preparation ofthe herb-containing composition is derived from the stems of the E.arvense herb and standardized for silica content (i.e., E. arvense stemextract preparation). Briefly, stem parts of the E. arvense herb areremoved from the plant and dried. They are then measured for a minimumof 2.5% silicon content via HPLC analysis before being accepted for theextraction process. An extract was obtained using 65% (v/v)ethanol/water extraction solvent. The extract was concentrated to aratio of approximately 4:1. The extract is then tested again for minimum3% silicon content via HPLC. The final extract dry concentrate appearedas a fine brown powder with a characteristic odor and taste.

In another embodiment, the E. arvense herb preparation is standardizedto organic silicon by a solvent extraction process. Briefly, stem partsof the E. arvense herb are removed from the plant and dried.Morphological examination of the starting biomass (this includes bothmicroscopic and macroscopic characteristics) can help facilitate usingthe correct species (e.g., an authenticated voucher specimen is storedon file for species identification). An extract is obtained using hotwater (between about 50° C. and about 100° C.) as a solvent. The extractis concentrated to a ratio of approximately 5:1. The extract is thendried. The extract is tested for a minimum of approximately 3% siliconcontent via UV-Vis Spectrophotometry (silicon dioxide is used as areference substance). In one embodiment, if the extract falls outsidethe desired standards above, it is titrated with a dried extract thathad undergone the same process as above. The final extract dryconcentrate appear as a yellow-brown colored powder.

In one embodiment, the E. arvense herb preparation of theherb-containing composition is derived from the stems of the E. arvenseherb and standardized for total flavonoid content, i.e., E. arvense stemextract preparation.

In another embodiment, the E. arvense herb preparation is standardizedto flavonoid (expressed as isoquercetrin) content by a solventextraction process. Briefly, stem parts of the E. arvense herb areremoved from the plant and dried. They are then identified by TLC.(isoquercetrin is used as reference substance). Morphologicalexamination of the starting biomass (this included both microscopic andmacroscopic characteristics) can help facilitate using the correctspecies (e.g., an authenticated voucher specimen was stored on file forspecies identification). An extract was obtained using hot water(between about 50° C. and about 100° C.) as a solvent. The extract isconcentrated to a ratio of approximately 5:1. The extract is then dried.The extract is tested for a minimum of approximately 0.01% isoquercetrinvia UV-Vis Spectrophotometry (isoquercetrin is used as referencesubstance). If the extract falls outside the desired standards above, itis titrated with a dried extract that had undergone the same process asabove. The final extract dry concentrate appears as a yellow-browncolored powder.

In one embodiment, the E. arvense herb preparation is standardized toorganic silicon content and flavonoid content (expressed asisoquercetrin) using the methods described above.

In some embodiments, it is C. nurvala and/or L. aggregata, and not E.arvense, that is standardized. In some other embodiments, all of thethree are standardized. In some other embodiments, none of the three isstandardized. For example, the herb-containing composition can comprisestandardized C. nurvala and not standardized E. arvense and L.aggregata. Alternatively, the composition can comprise standardized E.arvense and not standardized C. nurvala and L. aggregata. Alternatively,the composition can comprise standardized L. aggregata and notstandardized C. nurvala and E. arvense. In one embodiment, thecomposition can comprise standardized C. nurvala and E. arvense and notstandardized L. aggregata. Alternatively, the composition can comprisestandardized C. nurvala and L. aggregata, and not standardized E.arvense. Alternatively, the composition can comprise standardized E.arvense and L. aggregata, and not standardized C. nurvala. Thestandardization can be accomplished via any suitable compound, such assilicon, saponins, tannins, lupeol, etc. For example, the Cratevanurvala extract preparation can be standardized to have at least one ofthe following based on total weight of the Crateva nurvala root extractpreparation: (i) saponins not less than 25%; (ii) tannins not less than2%; and (iii) lupeol not less than 1.5%.

Other Constituents

The herb-containing compositions described herein can includeconstituents in addition to the herbal constituents C. nurvala, E.arvense, and L. aggregata. For example, in one embodiment, thecomposition can contain silicon, such as in the form of silica, such asanhydrous silica. The additional silicon assists with urogenital tissuesupport, strengthening and firmness. In one embodiment, theherb-containing composition contains from about 10 mg dry weightequivalents to about 71 mg dry weight equivalents of total silicon peroral dosage unit. In another embodiment, the herb-containing compositioncontains from about 15 mg dry weight equivalents to about 45 mg dryweight equivalents of total silicon per oral dosage unit. In anotherembodiment, the herb-containing composition contains from about 28 mgdry weight equivalents to about 34 mg dry weight equivalents of totalsilicon per oral dosage unit.

In another embodiment, the herb-containing composition containsphosphorus. In one embodiment, the herb-containing composition containsfrom about 5 mg dry weight equivalents of phosphorus to about 60 mg dryweight equivalents of phosphorus per oral dosage unit. In anotherembodiment, the herb-containing composition contains from about 10 mgdry weight equivalents of phosphorus to about 50 mg dry weightequivalents of phosphorus per oral dosage unit. In another embodiment,the herb-containing composition contains from about 20 mg dry weightequivalents of phosphorus to about 30 mg dry weight equivalents ofphosphorus per oral dosage unit.

In another embodiment, the herb-containing composition contains calcium.In one embodiment, the herb-containing composition contains from about 1mg dry weight equivalents of calcium to about 30 mg dry weightequivalents of calcium per oral dosage unit. In another embodiment, theherb-containing composition contains from about 5 mg dry weightequivalents of calcium to about 25 mg dry weight equivalents of calciumper oral dosage unit. In another embodiment, the herb-containingcomposition contains from about 10 mg dry weight equivalents of calciumto about 20 mg dry weight equivalents of calcium per oral dosage unit.

In another embodiment, the herb-containing composition containsmagnesium. In one embodiment, the herb-containing composition containsfrom about 1 mg dry weight equivalents of magnesium to about 30 mg dryweight equivalents of magnesium per oral dosage unit. In anotherembodiment, the herb-containing composition contains from about 5 mg dryweight equivalents of magnesium to about 25 mg dry weight equivalents ofmagnesium per oral dosage unit. In another embodiment, theherb-containing composition contains from about 10 mg dry weightequivalents of magnesium to about 20 mg dry weight equivalents ofmagnesium per oral dosage unit.

The herb-containing composition can take any suitable form, depending onthe application. For example, the composition can be a part of a cream.In one embodiment, the herb-containing composition contains from about 1mg to about 100 mg dry weight equivalents C. nurvala stem/bark extractper gram of cream. In another embodiment, the herb-containingcomposition contains from about 10 mg to about 60 mg dry weightequivalents C. nurvala stem/bark extract per gram of cream. In anotherembodiment, the herb-containing composition contains from about 40 mg toabout 60 mg dry weight equivalents C. nurvala stem/bark extract per gramof cream.

In another embodiment, the herb-containing composition contains fromabout 1 mg to about 60 mg dry weight equivalents E. arvense herb pergram of cream. In another embodiment, the herb-containing compositioncontains from about 5 mg to about 40 mg dry weight equivalents E.arvense herb per gram of cream. In another embodiment, theherb-containing composition contains from about 10 mg to about 30 mg dryweight equivalents E. arvense herb per gram of cream.

In one embodiment, the herb-containing composition contains orange oil.In one embodiment, the herb-containing composition contains from about 1mg to about 30 mg orange oil per gram of cream. In another embodiment,the herb-containing composition contains from about 5 mg to about 25 mgdry orange oil per gram of cream. In another embodiment, theherb-containing composition contains from about 8 mg to about 12 mgorange oil per gram of cream.

In one embodiment, the herb-containing composition contains Juniperusvirginiana (Cedarwood) stem essential oil. In one embodiment, theherb-containing composition contains from about 1 μg to about 1,000 μgJ. virginiana stem essential oil per gram of cream. In anotherembodiment, the herb-containing composition contains from about fromabout 250 μg to about 750 μg J. virginiana stem essential oil per gramof cream. In another embodiment, the herb-containing compositioncontains from about 400 μg to about 600 μg J. virginiana stem essentialoil per gram of cream.

In one embodiment, the herb-containing composition contains Myrrh oil.In one embodiment, the herb-containing composition contains from about 1μg to about 1,000 μg Myrrh oil per gram of cream. In another embodiment,the herb-containing composition contains from about from about 250 μg toabout 750 μg Myrrh oil per gram of cream. In another embodiment, theherb-containing composition contains from about 400 μg to about 600 μgMyrrh oil per gram of cream.

In one embodiment, the herb-containing composition contains Orangeflower oil. In one embodiment, the herb-containing composition containsfrom about 1 μg to about 1,000 μg Orange flower oil per gram of cream.In another embodiment, the herb-containing composition contains fromabout from about 250 μg to about 750 μg Orange flower oil per gram ofcream. In another embodiment, the herb-containing composition containsfrom about 400 μg to about 600 μg Orange flower oil per gram of cream.

In one embodiment, the herb-containing composition contains Cupressussempervirens (Cypress) leaf oil. In one embodiment, the herb-containingcomposition contains from about 1 μg to about 1,000 μg C. sempervirensleaf oil per gram of cream. In another embodiment, the herb-containingcomposition contains from about from about 50 μg to about 500 μg C.sempervirens leaf oil per gram of cream. In another embodiment, theherb-containing composition contains from about 75 μg to about 125 μg C.sempervirens leaf oil per gram of cream.

In another embodiment, the herb-containing composition containsd-alpha-tocopheryl acetate (Natural Vitamin E). In one embodiment theherb-containing composition contains d-alpha-tocopheryl acetate. In oneembodiment, the herb-containing composition contains from about 0.1 mgto about 25 mg d-alpha-tocopheryl acetate per gram of cream. In anotherembodiment, the herb-containing composition contains from about 1 mg toabout 10 mg dry d-alpha-tocopheryl acetate per gram of cream. In anotherembodiment, the herb-containing composition contains from about 4 mg toabout 6 mg d-alpha-tocopheryl acetate per gram of cream.

In another embodiment, the herb-containing composition containsdiazolidinylurea. In one embodiment, the herb-containing compositioncontains diazolidinylurea. In one embodiment, the herb-containingcomposition contains from about 0.1 mg to about 10 mg diazolidinylureaper gram of cream. In another embodiment, the herb-containingcomposition contains from about 1 mg to about 5 mg dry diazolidinylureaper gram of cream. In another embodiment, the herb-containingcomposition contains from about 3 mg to about 3.5 mg diazolidinylureaper gram of cream.

In another embodiment, the herb-containing composition containshydroxybenzoates. In one embodiment, the herb-containing compositioncontains hydroxybenzoates. In one embodiment, the herb-containingcomposition contains from about 0.1 mg to about 5 mg hydroxybenzoatesper gram of cream. In another embodiment, the herb-containingcomposition contains from about 0.5 mg to about 3 mg dryhydroxybenzoates per gram of cream. In another embodiment, theherb-containing composition contains from about 1 mg to about 2 mghydroxybenzoates per gram of cream.

In another embodiment, the herb-containing composition contains extractsof C. nurvala stem/bark; E. arvense leaf/stem; and L. aggregata root;Orange oil; J. virginiana stem; Myrrh oil; Orange flower oil; C.sempervirens leaf; d-alpha-tocopheryl acetate; diazolidinylurea; andhydroxybenzoates.

Medicinal Properties and uses of Compositions

One embodiment provides herb-containing compositions useful in a methodof prophylaxis or treatment of disorders of the urogenital system, e.g.,urinary incontinence, enuresis (e.g., bed-wetting), benign prostatichyperplasia, overactive bladder, nocturia, urinary calculi, cystitis,and UTIs. Not to be bound by any particular theory, but in someembodiments the primary active ingredients present in both the Cratevaand Equisetum are the saponins and plant sterols. Crateva containsflavonoids, glucosinolates and the plant sterol, lupeol, while Equisetumcontains the mineral, silica, flavonoids (isoquercetin, luteolin, andkaempferol) and the saponin, equisetin. Nadkarni K. M. et al., IndianMateria. Medica. Bombay Popular Prakashan; British Herbal Pharmacopeia.Publ: British Herbal Medicine Association 1983; Bone K. ClinicalApplications of Ayurvedic and Chinese Herbs. Monographs for the westernherbal practitioner. Phytotherapy Press, Warwick, Qld, Australia 1997;The German Commission E Monographs, 1998; D'Agostino M. et al., Boll.Soc. Ital. Biol. Sper., 30;60(12):2241-5 (1984); Pengelly A. Theconstituents of medicinal plants: an introduction to the chemistry andtherapeutics of herbal medicine. Sunflower Herbal 2^(nd) Edition,Merriwa, NSW, Australia, 1996; Lakshmi V. et al., Planta Medica, 32:214-216 (1977).

In one embodiment, the herb-containing compositions can be useful in theprevention and treatment of urinary calculi. Crateva and Equisetum havebeen shown to alter urinary electrolytes in such a way so as to reducelithogenic potentiality. Varalakshmi P et al., J. Ethnopharmacology, 28:313-321 (1990); Anand R. et al., Indian J. Pharmacology, 27: 265-268(1995); Grases F. et al., Int. Urol. Nephrol., 26(5):507-511 (1994).Crateva has also been found to inhibit small intestinal Na—K-ATPase.Varalakshmi P. et al., J. Ethnopharmacology, 31: 67-73 (1991). Theseeffects may be due primarily to the presence of the sterol lupeol. Anumber of studies have shown that lupeol has anti-oxaluric andanti-calcuric effects leading to increased spontaneous passing of stonesand symptomatic relief. Varalakshmi P et al., J. Ethnopharmacology, 28:313-321 (1990); Anand R. et al., Indian J. Pharmacology, 27: 265-268(1995); Malini M. M., et al., Jpn. J. Med. Sci. Biol., 48(5-6):211-20(1995); Lakshmi V. et al., Planta Medica, 32: 214-216 (1977).

In one embodiment, it is hypothesized that this passage of the stone maybe produced via a tonic contractile action of the drug on the smoothmuscle. Varalakshmi P et al., J. Ethnopharmacology, 28: 313-321 (1990);Anand R. et al., Indian J. Pharmacology, 27: 265-268 (1995); DeshpandeP. J. et al., Indian J. Med. Res., 76(Suppl): 46-53 (1982). Equisetummay also assist with incontinence via a similar mechanism. Kaempferol,luteolin and isoquercetin, found in Equisetum are documented to inhibitxanthine oxidase and subsequent urate calculi formation. Nagao A. etal., Biosci. Biotechnol. Biochem., 63(10):1787-90 (1999). These herbaldrugs can act to improve the tone of the bladder wall. In 1982,Deshpande et al. reported that Crateva has beneficial effects onneurogenic bladder and post-prostatectomic atony of the bladder.Deshpande P. J. et al., Indian J. Med. Res., 76(Suppl):46-53 (1982).

In one embodiment, the herb-containing compositions can be useful in theprevention and treatment of incontinence and benign prostatichypertrophy and urinary incontinence. Crateva administration produces amarked relief of symptoms of frequency, incontinence, pain and retentionof urine in men with hypotonic bladder as a result of benign prostatichypertrophy. Deshpande P. J. et al., Indian J. Med. Res., 76(Suppl):46-53 (1982). Crateva can act to increase the tone of thebladder and the expulsive force of urine, thereby helping effectiveevacuation. Deshpande P. J. et al., Indian J. Med. Res., 76(Suppl):46-53 (1982)—cystometric studies analyzed in this paper alsoshow that Crateva normalizes the tone of the urinary bladder andsignificantly decreases residual urine volume. The herb-containingcompositions provided herein, therefore, are useful in the preventionand treatment of urinary incontinence.

These results are also supported by animal studies where Crateva hasbeen shown to increase the tone of both smooth and skeletal muscle invitro. Das P. K. et al., J. Res. Ind. Med., 9:49 (1974). Animal studiesshow that 40 days of treatment with Crateva resulted in hypertoniccurves of the urinary bladder when compared to initial curves. Das P. K.et al., J. Res. Ind. Med., 9:49 (1974).

Equisetum is rich in silicic acid and silicates. In one embodiment,silica supports the regeneration of connective tissue. Chevallier, A.,The Encyclopedia of Medicinal Plants, (Horn V. and Weil, C., Eds.)Dorling Kindersley Ltd., London (1996). Thus, the herb-containingcompositions described herein can be useful in the prophylaxis ortreatment of disorders of the urogenital system, for example, urinaryincontinence, enuresis (e.g., bed-wetting), benign prostatichyperplasia, urinary calculi, cystitis, and UTIs.

The herb-containing compositions provided herein are useful in theprevention and treatment of UTIs and cystitis. It has been shown in ratstudies that some species of the Equisetum family have a diureticaction, shown by excretion of sodium, potassium and chloride, similar tothat of other drugs such as hydrochlorothiazide. Perez Gutierrez R. M.et al., J. Ethnopharmacol., 14(2-3):269-272 (1985); D'Agostino M. etal., Boll. Soc. Ital. Biol. Sper., 60(12):2241-5 (1984). A more recentstudy using rats also demonstrated beneficial affects of the drugs inurolithiasis. Grases F. et al., Int. Urol. Nephrol., 26(5):507-511(1994). These authors suggest that this result could be due to theantibacterial action of the constituents, namely, the saponins.Interestingly, Crateva has anti-inflammatory and antibacterialproperties. Nadkarni K. M. et al., Indian Materia Medica. Bombay PopularPrakashan; Bone K. Clinical Applications of Ayurvedic and Chinese Herbs.Monographs for the western herbal practitioner. Phytotherapy Press,Warwick, Qld, Australia 1997; Salvat A. et al., Lett. Appl.Microbiology, 32(5): 293-7 (2001); Xu H X et al., Phytother. Res.,15(1):39-43 (2001); Geetha T. et al., Gen. Pharmacol., 32(4):495-7(1999); Geetha T. et al., J. Ethnopharmacol., 76(1):77-80 (2001).Combined with Crateva's tonic effects on smooth muscle, it is consideredto assist with bladder evacuation, thereby decreasing residual urine, aknown to contributing factor to UTIs. Deshpande P. J. et al., Indian J.Med. Res., 76(Suppl):46-53 (1982).

Isoquercetin, found in Equisetum, is known to have anti-inflammatoryeffects via inhibition of inflammatory prostaglandins, although Cratevais thought to produce anti-inflammatory effects via a differentmechanism. D'Agostino M. et al., Boll. Soc. Ital. Biol. Sper.,30;60(12):2241-5 (1984); Geetha T. et al., Gen. Pharmacol., 32(4):495-7(1999). The positive effect on chronic urinary tract infections is mostlikely a combination of anti-bacterial and anti-inflammatory actions.

In one embodiment, the herb-containing compositions can be useful in theprevention and treatment of urinary incontinence, UTIs, and enuresis.There is evidence for the use of Virginia cedarwood in treatingincontinence, enuresis and assisting bladder tone as well as bladderinfections, difficult urination and cystitis. Tisserand and Balacs,Essential Oil Safety. A Guide for Health Care Professionals. ChurchillLivingstone, U. K., 1995; 28-29, 31, 33-34; Price, S. PracticalAromatherapy. Thorsons, Harper Collins Publishers, California, U.S.,1983; 157-8, 170-171, 174, 185; Davis, P. Aromatherapy An A-Z. The C. W.Daniel Company, Essex, England, 1998; 194; Valnet, J. The Practice ofAromatherapy. Saffron Walden, The C. W. Daniel Company, Essex, England,1980; 120-121; Price, S. The Aromatherapy Workbook. Thorsons (HarperCollins), California, USA, 1993; 67; Caddy, R., Aromatherapy EssentialOils in Colour. Amberwood Publishing Ltd, East Horsley, Surrey, England,1997; 14. The documented properties likely to produce this effectinclude the antispasmodic, diuretic, antiseptic and astringent.

Cypress is documented as an antispasmodic, astringent, antiseptic,deodorant, diuretic and tonic that may promote venous circulation to thekidneys and bladder area, improve bladder tone and assist with urinaryincontinence and enuresis. Tisserand and Balacs, Essential Oil Safety. AGuide for Health Care Professionals. Churchill Livingstone, U. K., 1995;28-29, 31, 33-34; Valnet, J. The Practice of Aromatherapy. SaffronWalden, The C. W. Daniel Company, Essex, England, 1980; 120-121, Holmes,P. The Energetics of Western Herbs. Artemis Press, Boulder, Colo., USA,1989; 567-569, 792; Damian, P & K. Aromatherapy Scent and Psyche.Healing Arts Press, Rochester, Vermont, Canada, 1995; 187-188; Price, S.The Aromatherapy Workbook. Thorsons (Harper Collins), California, USA,1993; 67; Chidell, L. Aromatherapy. A Definitive Guide to EssentialOils. Hodder and Stoughton Ltd, Kent, UK, 1992; 23-24, 80-81; Keller, E.The Compete Home Guide to Aromatherapy. H J Kramer, Inc, Tiburon,Calif., USA, 1991; 178-179.

Recent literature describes Myrrh as an astringent and antiseptic thatproduces a soothing effect on mucous membranes of the urinary system andpromotes healing of tissues. Battaglia, S. The Complete Guide toAromatherapy. The Perfect Potion Pty Ltd, Virginia, Brisbane, Qld,Australia, 1995; 110-113, 116, 150-151, 158-159, 182-183, 184-185, 187;Lawless, J. The Encyclopaedia of Essential Oils. (1992) Element Booksfor Jacaranda Wiley, Ltd, Australia, 1992; 76-77, 88-89, 135-136. Orangeand Neroli are documented as having antispasmodic, antiseptic anddeodorant effects. 6,10; Sheppard-Hanger. The Aromatherapy PractitionerManual. Aquarius Publishing, Willetton, Western Australia, 1995; 183;Sellar, W. The Directory of Essential Oils. Saffron Walden, The C.W.Daniel Company, Essex, England, 1992; 50-51, 106-107; Keller, E. TheCompete Home Guide to Aromatherapy. H J Kramer, Inc, Tiburon, Calif.,USA, 1991; 178-179.

In one embodiment, the herb-containing compositions can be useful in theprevention and treatment of disorders of the prostate, e.g., benignprostatic hyperplasia. Essential oils are also recommended for malereproductive health, indicating a possible effect on the prostate inmen. Battaglia, S. The Complete Guide to Aromatherapy. The PerfectPotion Pty Ltd, Virginia, Brisbane, Qld, Australia, 1995; 110-113, 116,150-151, 158-159, 182-183, 184-185, 187; Price, S. PracticalAromatherapy. Thorsons, Harper Collins Publishers, California, U.S.,1983; 157-8, 170-171, 174, 185; Lawless, J. The Encyclopaedia ofEssential Oils. (1992) Element Books for Jacaranda Wiley, Ltd,Australia, 1992; 76-77, 88-89, 135-136; Valnet, J. The Practice ofAromatherapy. Saffron Walden, The C. W. Daniel Company, Essex, England,1980; 120-121.

Certain drugs commonly prescribed for urinary incontinence, such asoxybutynin hydrochloride, inhibit the muscarinic action of acetylcholineon smooth muscle, producing a direct antispasmodic action; that is, theyrelax the detrusor muscle. Tapp A. J. S. et al., Brit. J. Obstetrics andGynecology; 97: 521-6 (1990). This antispasmodic effect is preferred tothe anticholinergic effect of drugs previously used for patients withurinary incontinence. The antispasmodic effect of these essential oils,whilst not provided in more specific detail, may also be producing anaction similar to currently prescribed drug medications.

Herbal diuretics are documented as increasing blood flow through thekidneys without resorption at the distal tubule of the nephron andassociated loss of electrolytes (apart from potassium), as is the casewith more sophisticated modern drug diuretics. Mills and Bone,Principles and Practice of Phytotherapy. Churchill Livingstone, 2000;35, 220-222. Also, diuresis often does not result from herbal diureticuse. Mills and Bone, Principles and Practice of Phytotherapy. ChurchillLivingstone, 2000; 35, 220-222. Not to be bound by any particulartheory, but it may be that these herbal essential oils largely stimulatethe blood flow to the kidneys resulting in an increase or greaterefficiency in the production of urine. This effect, when combined withcomplete emptying of the bladder when voiding, may minimize the volumeof urine lost through continual leakage.

Pharmaceutical Compositions and Formulations

One embodiment provides methods of preventing and/or treating aurogenital system disorder in a subject by administering to the subjectan herb-containing composition in an amount sufficient to prevent ortreat the urogenital system disorder (i.e., pharmaceutically effectiveamount). The composition can be any of the compositions describedherein. A subject in need of the presently described composition (andthe administration thereof) can be one suffering any of the urogenitalsystem disorders, including at least one of (i) urinary incontinence and(ii) overactive bladder symptoms. For example, the urogenital systemdisorder can include urinary incontinence, enuresis, benign prostatichyperplasia, nocturia, urinary calculi, cystitis, OAB, a urinary tractinfection, and the like.

In one embodiment, the herb-containing compositions can be used alone orfurther formulated with pharmaceutically acceptable compositions,vehicles, or adjuvants with a favorable delivery profile (i.e., suitablefor delivery to a subject, particularly one in need thereof). Suchcompositions typically comprise the herb-containing composition and apharmaceutically acceptable carrier. “Pharmaceutically acceptablecarrier” in some embodiments is intended to include any and allsolvents, dispersion media, coatings, antibacterial and antifungalcompositions, isotonic and absorption delaying compositions, and thelike, compatible with pharmaceutical administration. Suitable carriersare described in the most recent edition of Remington's PharmaceuticalSciences, a standard reference text in the field, which is incorporatedherein by reference. Preferred examples of such carriers or diluentsinclude, but are not limited to, water, saline, Ringer's solutions,dextrose solution, and 5% human serum albumin. The use of such media andcompositions for pharmaceutically active substances is well known in theart. Except insofar as any conventional media or composition isincompatible with the active composition, use thereof in thecompositions is contemplated. Supplementary active compositions can alsobe incorporated into the compositions.

A pharmaceutical composition is formulated to be compatible with itsintended route of administration. Examples of routes of administrationinclude, e.g., oral; transdermal (i.e., topical), and transmucosaladministration. The pH can be adjusted with acids or bases, such ashydrochloric acid or sodium hydroxide.

Oral compositions generally include an inert diluent or an ediblecarrier. They can be enclosed in gelatin capsules, caplets or compressedinto tablets. For the purpose of oral therapeutic administration, theherb-containing composition can be incorporated with excipients and usedin the form of tablets, troches, or capsules. Oral compositions can alsobe prepared using a fluid carrier for use as a mouthwash, wherein thecomposition in the fluid carrier is applied orally and swished andexpectorated or swallowed. Pharmaceutically compatible bindingcompositions, and/or adjuvant materials can be included as part of thecomposition. The tablets, pills, capsules, troches and the like cancontain any of the following ingredients, or compositions of a similarnature: a binder such as microcrystalline cellulose, gum tragacanth orgelatin; an excipient such as starch or lactose, a disintegratingcomposition such as alginic acid, Primogel, or corn starch; a lubricantsuch as magnesium stearate or Sterotes; a glidant such as colloidalsilicon dioxide; a sweetening composition such as sucrose or saccharin;or a flavoring composition such as peppermint, methyl salicylate, ororange flavoring. The herb-containing compositions provided herein canalso be formulated as a topical cream for transdermal or transmucosaladministration.

In one embodiment, the herb-containing compositions are prepared withcarriers that will protect the composition against rapid eliminationfrom the body, such as a controlled release formulation, includingimplants and microencapsulated delivery systems. Biodegradable,biocompatible polymers can be used, such as ethylene vinyl acetate,polyanhydrides, polyglycolic acid, collagen, polyorthoesters, andpolylactic acid. Methods for preparation of such formulations will beapparent to those skilled in the art. The materials can also be obtainedcommercially from Alza Corporation and Nova Pharmaceuticals, Inc.

The pharmaceutical compositions can be included in a container, pack, ordispenser together with instructions for administration.

As a result of administrating the presently described herb-containingcomposition to a subject in need thereof, the symptoms in the subjectcan be alleviated. For example, the treatment can result in a reductionin at least one of (i) urinary incontinence and (ii) OAB. In oneembodiment, the treatment can result in an improvement of at least oneof average daily frequency of urination; average nightly frequency ofurination; total urinary incontinence episodes; stress incontinenceepisodes; and urinary urgency episodes.

In contrast to some of the pre-existing herb-containing compositions,the compositions provided herein surprisingly can provide efficacy andefficiency much higher that the pre-existing compositions. For example,the compositions provided herein can result in improvement that is aboutat least two times, such as at least three times, four times, fivetimes, or more, as fast as the pre-existing herb-containingcompositions. For example, compared to the composition as provided inU.S. Pat. No. 7,378,115, which achieved improvement in about 3 months,the compositions provided herein can achieve a comparable level ofimprovement in less than three months, such as less than two months,such as less than one month, such as less than 2 weeks. In oneembodiment, the presently described composition can accomplish theimprovement between about two weeks and about two months, such as abouttwo weeks, or such as about one month.

The articles “a” and “an” are used herein to refer to one or to morethan one (i.e., to at least one) of the grammatical object of thearticle. By way of example, “a polymer resin” means one polymer resin ormore than one polymer resin. Any ranges cited herein are inclusive. Theterms “substantially” and “about” used throughout this Specification areused to describe and account for small fluctuations. For example, theycan refer to less than or equal to ±5%, such as less than or equal to±2%, such as less than or equal to ±1%, such as less than or equal to±0.5%, such as less than or equal to ±0.2%, such as less than or equalto ±0.1%, such as less than or equal to ±0.05%.

REFERENCES

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2. Anand R, Patnaik G K, Kamal Roy, Bhaduri A P, 1995. Antioxaluric andanticalciuric activity of lupeol derivatives. Indian Journal ofPharmacology; 27: 265-268.

3. Grases F, Melero G. Costa-Bauza A, Prieto R, March J G, 1994.Urolithiasis and phytotherapy. International Journal of Urology andNephrology; 26(5): 507-511.

4. Varalakshmi P, Shamila Y, Latha E. Effect of Crateva nurvala inexperimental urolithiasis. J Ethnopharmacology 1990; 28: 313-321.

5. Malini M M, Baskar R, Varalakshmi P. Effect of lupeol, a pentacyclictriterpene, on urinary enzymes in hyperoxaluric rats. Jpn J Med Sci Biol1995 October-December; 48(5-6): 211-20.

6. Das P K, Rathor R S, Lal R, Tripathi R M, Ram A K, Biswas M, 1974.Anti-inflammatory and anti-arthritic activity of Varuna. Journal ofResearch of Indian Medicine; 9:49.

7. Nagao A, Seki M, Kobayashi H, 1999. Inhibition of xanthine oxidase byflavonoids. Biosci Biotechnology Biochemistry; 63(10): 1787-90.

8. Steels E, Ryan J, Seipel T, Rao A, 2002. Crateva and Equisetum reduceurinary incontinence symptoms. Australian Continence Journal; 8 (3).

9. Schauss A G, Spiller G, Chaves S, Gawlicka A, 2006. Reducing thesymptoms of overactive bladder and urinary incontinence: results of atwo-month, double-blind, placebo-controlled clinical trial. Posterpresentation FASEB, San Francisco, April, 2006.

10. Robinson D, Pearce K F, Preisser J S, Dugan E, Suggs P K and Cohen SJ, 1998. Relationship between patient reports of urinary incontinencesymptoms and quality of life measures. Obstetrics and Gynaecology; 91(2): 224-228.

11. Coyne K, Payne C, Bhattacharyya S, Revicki D, Thompson C, Corey R,Hunt T, 2004. The impact of urinary urgency and frequency onhealth-related quality of life in overactive bladder: Results from anational community survey. Value in Health; 7(4)

12. Bone K. Clinical Applications of Ayurvedic and Chinese Herbs, 1997.Monographs for the western herbal practitioner. Phytotherapy Press,Warwick, Queensland, Australia.

13. Geetha T, Varalakshmi P, 2001. Anti-inflammatory activity of lupeoland lupeol linoleate in rats. Journal of Ethnopharmacology; 76(1): 77-80

14. Geetha T, Varalakshmi P, 1999. Anticomplement activity oftriterpenes from Crateva nurvala stem bark in adjuvant arthritis inrats. General Pharmacology; 32(4):495-7.

15. Chan Wang, Yue Dai, Jian Yang, Guixin Chou, Changhong Wang, ZhengtaoWang, 2007. Treatment with total alkaloids from Radix Linderae reducesinflammation and joint destruction in type II collagen-induced model forrheumatoid arthritis. Journal of Ethnopharmacology; 111:322-328.

16. Yubin Luo, Mei Liu, Xiujuan Yao, Yufeng Xia, Yue Dal, Guixin Chouand Zhengtao Wang, 2009. Total alkaloids from Radix Linderae prevent theproduction of inflammatory mediators in lipopolysaccharide-stimulatedRAW 264.7 cells by suppressing NF-κB and MAPKs activation. Cytokine;46(1): 104-110.

17. Qinglin L, Guixin C, Changgui D, Zhengtao W, Fang H, 1997-12.Studies on the analgesic and anti-inflammatory action of radix Linderaeextract. Journal of Chinese Medicinal Materials. (China PharmaceuticalUniversity, Nanjing 210038) (Abstract)

18. Runwei Yan, Yang Yang, Yingying Zeng, Guolin Zou, 2009. Cytotoxicityand antibacterial activity of Lindera strychnifolia essential oils andextracts. Journal of Ethnopharmacology; 121: 451-455.

19. Nagaraj M, Sunitha S, Varalakshmi P, 2000. Effect of lupeol, apentacyclic triterpene, on the lipid peroxidation and antioxidant statusin rat kidney after chronic cadmium exposure. Journal of AppliedToxicology; 20(5): 413-417.

20. Ohno T, Takemura G, Murata I, Kagawa T, Akao S, Minatoguchi S,Fujiwara T and Fujiwara H, 2005. Water extract of the root of Linderastrychnifolia slows down the progression of diabetic nephropathy indb/db mice. Life Sciences; 77(12):1391-1403.

21. Bensky D and Gamble A, 1993. Chinese Herbal Materia Medica, RevisedEdition. England Press, Seattle, Wash., USA.

22. Shimomura M, Ushikoshi H, Hattori A, Murata I, Ohno Y, Aoyama T,Kawasaki M, Nishigaki K, Takemura G, Fujiwara T, Fujiwara H, MinatoguchiS, 2010. Treatment with Lindera strychnifolia reduces blood pressure bydecreasing sympathetic nerve activity in spontaneously hypertensiverats. American Journal of Chinese Medicine; 38(3): 561-8.

23. Noda Y, Mori A, Anzai K, Packer L,1999. Superoxide anion radicalscavenging activity of Uyaka (Lindera strychnifolia), a natural extractused in traditional medicine. Antioxidant Food Supplements in HumanHealth.

24. Bin Li, Gil-Saeng Jeong, Dae-Gill Kang, Ho-Sub Lee and Youn-ChulKim, 2009. Cytoprotective effects of lindenenyl acetate isolated fromLindera strychnifolia on mouse hippocampal HT22 cells. European Journalof Pharmacology. Neuropharmacology and Analgesia; 16(1-3): 58-65.

The invention is further defined by reference to the following examples,which are not meant to limit the scope of the present invention. It willbe apparent to those skilled in the art that many modifications, both tothe materials and methods, may be practiced without departing from thepurpose and interest of the invention.

NON-LIMITING WORKING EXAMPLES Example 1 Clinical Trial ofHerb-Containing Natural Therapeutic Combination for Urinary Incontinenceand OAB (Overactive Bladder) Symptoms General

Studies were conducted to investigate the effectiveness of anherb-containing natural therapeutic bladder control preparation inrelieving urinary incontinence and OAB (overactive bladder) symptoms(hereinafter, “UI/OAB bladder control preparation”). The interviews wereconducted at Kelvin Grove Natural Medicine clinic, Brisbane, Australia.

Materials and Methods

Test Preparation

The herbal components of bladder control preparation are listed on theARTG (Australian Register of Therapeutic Goods) as safe for use. Eachpreparation contained the herbs, C. nurvala stem/bark extract, E.arvense stem extract and L. aggregata root extract. For example, eachtablet contained dry weight equivalents as follows: C. nurvala stem/barkextract (3,000 mg) 3 g, E. arvense (Horsetail) herb (1,500 mg) 1.5 g,and L. aggregata (Lindera) root ((1,500 mg) 1.5 g.

Study Design

Nine (9) adults experiencing symptoms of urge incontinence and/or stressincontinence, OAB, urinary urgency, nocturia or urinary frequency on aregular basis were recruited through Kelvin Grove Natural Medicineclinic and advertisements in local health food stores. One participantdid not complete the study due to unrelated reasons. There were eight(8) participants (one male and seven females) completing the study withan average age of 58 years (range 45-80 years).

All participants met the following criteria:

-   -   had not undergone recent surgery particularly hysterectomy or        prolapse repair within the last 12 months,    -   did not have any serious health conditions such as diabetes        mellitus, heart disease, pancreatic disease, hepatic disease or        chronic inflammatory conditions,    -   were not currently being treated for psychotic disturbances, and    -   did not use any medicine for incontinence symptoms in the last        month prior to commencement of the study.

None of the participants were engaging in the specific pelvic exercisesto improve muscle tone prior to the study.

The treatment protocol consisted of ingesting once daily, a prescribedherbal blend equivalent to dry extracts of 6 g C. nurvala, 3 g E.arvense, and 3 g L. aggregata daily over a period of two months. Averagedaily and nightly (nocturia) frequency of urination, total urinaryincontinence episodes, stress incontinence episodes and urinary urgencyepisodes were assessed, compared to baseline, at 2 weeks, one month, andagain at two months. These results were compared using a paired t-test.

Efficacy of treatment was also assessed, compared to baseline and onemonth by using the short versions of the Incontinence ImpactQuestionnaire (IIQ) and the Urogenital Distress Inventory (UDI). Theshort version (six questions) of the IIQ assesses the impact ofincontinence on daily activities, such as household chores, physicalactivity and social activities. The questions in the UDI relatespecifically to the physical aspects of incontinence and bladder controlas detailed below in Table 3.

TABLE 3 Urogenital Distress Inventory Do you experience, and if so, howmuch are you bothered by: Frequent urination Leakage due to feeling orurgency Leakage due to activity, coughing, sneezing Small amounts ofleakage (drops) Difficulty empting bladder Pain or discomfort in lowerabdominal or genital area

The short version (six questions) of the IIQ assesses the impact ofincontinence on daily activities, such as household chores, physicalactivity and social activities as summarized below in Table 4.

TABLE 4 Incontinence impact questionnaire Has urine leakage affected thefollowing: Household chores Physical recreation Entertainment activitiesTravel >30 min from home Social activities Emotional health Feelingfrustrated

All questions were rated on a scale of 0 to 3 (0=not bothered,1=slightly bothered, 2=moderately bothered, 3=extremely bothered). Bothquestionnaires were standardized disease specific questionnaires used todetect bothersome incontinence in older people. Robinson, D. et al.,Obstetrics and Gynecology, 91:2, 224-8 (1998).

A positive improvement was defined as a statistically significantdifference, i.e., p-value≦0.05, in a parameter measuring the physicalaspects of incontinence or the physical or social activities of testsubjects receiving the UI/OAB bladder control preparation when comparedto the same parameter in human test subjects prior to receiving theUI/OAB bladder control preparation. A positive improvement in anyparameter relating to the physical aspects of incontinence or overactivebladder or the physical or social activities of human test subjectsreceiving UI/OAB bladder control preparation when compared to the sameparameter in human test subjects prior to receiving the bladder controltest preparation demonstrates that the UI/OAB bladder controlpreparation is useful to prevent or treat a urogenital system disorderin a human subject, e.g., urinary incontinence; overactive bladder;enuresis; benign prostatic hyperplasia; nocturia; urinary calculi;cystitis; and urinary tract infection.

Results and Discussion

Frequency of Urination During the Day

The results demonstrated that the average frequency of urination duringthe day reduced significantly (p<0.005) during the two months oftreatment. The number of times participants needed to empty the bladderreduced from an average of 12.4 (prior to treatment), to 9.8 times perday (after 2 weeks), 8 times per day (after one month), which is withinthe normal range, and 7.6 times per day (after two months).

Frequency of Nocturia

The results demonstrated that this treatment was effective in reducingthe number of times participants needed to empty the bladder at night.There was a reduction in awakenings from 2.75 times per night initiallyto 0.625 times and 0.375 times and 0.313 times per night at two weeksand month 1 and month 2 respectively (all p values<0.05). Many of theparticipants were able to sleep though the night altogether after twoweeks of treatment. In addition some participants commented that if theyawoke with the need to urinate, they could hold the urine and return tosleep without having to get out of bed and without accident.

Urinary Urgency

The results demonstrated that urinary urgency reduced from an average of3.75 times a day to 2.5 times (p<0.05) at week 2 and 1.4 times (p<0.05)at month 1 and 1.25 times (p<0.05) at month 2.

Urinary Incontinence

The results demonstrated that this treatment was effective in reducingthe number of times participants experienced urinary incontinence. Therewas a reduction in incontinence episodes from 2 times per day initiallyto 0.5 times at 2 weeks and 0 times at month 1 and month 2 (p<0.05). A50% reduction in pad by month one usage was also seen; however, at themonth 1 stage some participants still elected to use a pad as aprecautionary measure. By month 2 only one participant was still usingpads.

The Urogenital Distress Inventory

At baseline, symptoms experienced by most participants and causingbother (FIGS. 1 and 2) were: leakage due to urgency (88%), frequenturination (75%), leakage due to activity (75%), small amounts of leakage(75%) urinary incontinence (75%) and nocturia (63%). The averagebothered rating results show (FIG. 3) that all symptoms were reduced byone month of treatment. There was a significant positive change afterone month of treatment, which continued at month 2 for frequenturination (p=0.007; 0.005), leakage due to urgency (p=0.003; 0.002) andleakage due to activity (p=0.007; 0.005). The average bothered ratingfor small amounts of leakage was positive at month 1 and 2 (p=0.007;0.003). The small regression in response seen at month 2 is likely dueto the changed activities during month 2 including increased driving forlong periods and camping in the rain.

The results of the questionnaire were analyzed using the paired t-test.There was a significant positive change after one month of treatment forfrequent urination (p=0.007), leakage due to urgency (p=0.003), leakagedue to activity (p=0.007), and small amounts of leakage (p=0.007).

Incontinence Impact Questionnaire

The activities that showed to be most impacted on by incontinence andOAB (FIG. 4) were: physical recreation, travel greater than 30 minutesfrom home and feeling frustrated, which were experienced by 63% ofparticipants

The results of the questionnaire were analyzed using the paired t-test(Table 5 and FIG. 4). The results clearly show that Quality of Life(assessed through difficulty in doing daily and social activities aswell as emotional health and feelings of frustration) are adverselyaffected by having the symptoms of incontinence. By month one there wasan improvement in the perception of the effect of incontinence onlifestyle and social activities, which continued to month 2 indicated bypositive changes in response to all questions, including the mostbothersome responses; physical recreation (p=0.014; 0.014), travelgreater than 30 minutes from home (p=0.007; 0.009) and feelingfrustrated (p=0.013; 0.013).

TABLE 5 Results of paired t-test (p-values) Urinary Distress Inventoryand Incontinence Impact Questionnaire Urinary Distress Inventory LeakageLeakage Small amounts Difficulty Frequent due to related to of leakageemptying Pain or T-test results Urination urgency activity (drops)bladder discomfort 0 vs 1 month * * * * Not Not significant significant0 vs 2 month * * * * Not Not significant significant Incontinence ImpactQuestionnaire Travel greater than Household Physical Entertainment 30min Social Emotional Feeling T-test results chores recreation activitiesfrom home activities health frustrated 0 vs 1 month * * * * Not * *significant 0 vs 2 months * * * * Not * * significant * = p values <0.05

Participants were also asked, at the month 1 interview, if the treatmenthad improved their Quality of Life. Overall, 88% reported an improvementin QOL, at month 2 this increased to 100%. These results clearlyindicate that there is a significant improvement in QOL for participantsthat experience relief or a reduction in the severity in the symptoms ofurinary incontinence and OAB, including frequency, nocturia, urgency andbladder discomfort.

Effectiveness of Other Urinary Incontinence and Overactive BladderTherapeutics

Earlier studies show that treatment with Crateva relieves incontinence,pain and retention of urine in men and that Crateva and Horsetailcombined improves symptoms of urinary incontinence and quality of life.Deshpande P. J. et al., Indian J. Med. Res., 76 (Suppl):46-53 (1982);Steels et al, ACJ (2002); Schauss et al, FASEB (2006).

Commonly prescribed drug medications for UI and OAB e.g., oxybutyninhydrochloride, primarily act to inhibit the muscarinic action ofacetylcholine on the smooth muscle of the bladder producing a directantispasmodic action to relax the detrusor muscle. Wada Y. et al., Arch.Int. Pharmacodyn. Ther., 330(1):76-89 (1995); Tapp A. J. S. et al.,Brit. J. Obstetrics Gynecology, 97: 521-6 (1990). These medications alsoproduce unwanted anticholinergic effects, such as dry mouth, blurredvision and constipation. Pathak A S, Aboseif S R. Overactive Bladder:Drug therapy versus nerve stimulation. Nat Clin Pract Urol,2(7):310-311, (2005). UI/OAB bladder control preparation was notassociated with any side effects.

Herbal medications have previously shown effectiveness for UI and OABwithout these unwanted anticholinergic side effects; however, theduration of treatment needed for these effects are two to three months.Steels et at ACJ (2002); Schauss et al, FASEB (2006). This study hasshown that UI/OAB bladder control preparation reduced symptoms of UI andOAB and improved quality of life within a 2 to 4 week timeframe.

Conclusion

The results of this study indicate that UI/OAB bladder controlpreparation was effective in reducing symptoms of urinary incontinenceand OAB, including frequency, nocturia, incontinence and urgency.Symptom relief occurred after two weeks of treatment, with the severityof symptoms reducing further at month 1. Earlier herbal combinations hadshown effectiveness over a 2 to 3 month period.

The UI/OAB bladder control preparation assessed in this trial wassuitable for both men and women, did not produce any anticholinergic orother major side effects and halved pad usage after one month oftreatment.

This study shows that the herbal combination of C. nurvala, E. arvenseand L. aggregata shows increased effectiveness in reducing symptoms ofUI and OAB and improving quality of life than previous herbalcombination formulations and within a shorter timeframe.

Example 2 Comparison of the Effectiveness of the Different HerbalFormulations (Formulation 3 and UI/OAB Bladder Control Preparation) foruse in the Prevention and Treatment of Urinary Incontinence andOveractive Bladder (OAB) General

The aim of this study was to compare the efficacy of two formulations,Formula 3 (as described above in Example 4 of U.S. Pat. No. 7,378,115)and UI/OAB test preparation (presently described compositions) intreating the symptoms of urinary incontinence and OAB by analysing theresults of the Incontinence Impact Questionnaire (IIQ) and theUrogenital Distress Inventory (UDI) and day and night time urinaryfrequency from each of the studies on the individual formulations.Formula 3 had an E. arvense extract standardized for silicon andflavonoid content combined with C. nurvala and minerals, as providedabove and in Example 4 of U.S. Pat. No. 7,378,115. UI/OAB bladdercontrol preparation uses a combination of non-standardized E. arvenseextract combined with C. nurvala and L. aggregata and was assessed inExample 1.

Study Design

In order to directly compare the effectiveness of the two differenttablet formulations, percent (%) reduction in frequency of urination andnocturia for each formulation were directly assessed and compared. Inaddition, bothered ratings for both questionnaires at month 1 werecompared. This method of analysis was used for comparison as month 0(baseline) values in each of the studies varied.

Results and Discussion

The results of the number (%) of people on each formula experiencingsymptoms at Month 1 was assessed and compared. Comparison of thefrequency of urination and nocturia indicate that UI/OAB bladder controlformula was more effective in reducing the frequency of urination duringthe day (35% reduction at month 1 for UI/OAB formula compared to 25%reduction at month 1 for Formula 3). UI/OAB formula was also superior toFormula 3 in reducing nocturia with an 86% reduction at month 1 comparedto 40% reduction at month 1 for Formula 3.

TABLE 6 Percent Decrease in Frequency of Urination Day Night UI/OABUI/OAB test Formula 3 test prep Formula 3 prep Month 0 vs 26 35 40 86Month 1

The results of the number (%) of people bothered by their symptoms wasalso assessed and compared. The results from the Urinary DistressInventory (UDI) indicate that the UI/OAB bladder control preparation hada higher effectiveness at month 1, as compared to Formula 3 (FIG. 5;Table 6).

UI/OAB test preparation showed a higher percentage reduction at month 1for frequent urination, leakage due to feeling of urgency and activityand small amounts of leakage (drops). Results for difficulty emptingbladder have been included; however, due to the low number ofparticipants experiencing this symptom for UI/OAB bladder controlformulation, the results were not significant.

Month 1 results for UI/OAB bladder control preparation were morecomparable to month 3 results for Formula 3, showing that UI/OAB bladdercontrol preparation produces results within a much shorter timeframe.

Comparison of the Incontinence Impact Questionnaire (IIQ) also indicatedthat UI/OAB bladder control preparation had a faster and better response(shown by reduction in symptoms) to all the QOL questions than Formula 3at month 1.

TABLE 7 Percent reduction in bothered rating of UDI for UI/OAB bladdercontrol preparation and Formula 3 at month 1 and Formula 3 at month 3UI/OAB BC Preparation Formula 3 Formula 3 Month 1 Month 1 Month 3Frequent Urination 69 6 71 Leakage due to urgency 71 26 74 Leakagerelated to activity 65 33 68 Small amounts of 73 28 66 leakage (drops)Difficulty in 66 18 63 emptying bladder

Conclusion

The results of this study indicate that UI/OAB bladder controlpreparation is safe and was not associated with major adverse reactions.It was effective in reducing symptoms of urinary incontinence and OAB,including frequency, nocturia, incontinence and urgency.

As suggested by the results in Table 7 and FIG. 5, UI/OAB bladdercontrol preparation gave symptom relief with the severity of symptomsreduction being faster and more marked than for Formula 3 at month 1 oftreatment. UI/OAB gave greater reduction in urinary frequency in the day35 versus 26% reduction) and nocturia (86 versus 40% reduction) atmonth 1. Results produced by UI/OAB bladder control preparation afterone month of treatment were comparable, and in some instances betterthan those produced by Formula 3 after 3 months of treatment.

In summary, UI/OAB bladder control formula, containing C. nurvala, E.arvense and L. aggregata showed improved and faster effectiveness inreducing symptoms of urinary incontinence and OAB when compared toearlier herbal combinations shown to be effective in this area. Thiscombination of C. nurvala, and L. aggregata with non-standardized E.arvense showed superior results over the Formula 3 containing C.nurvala, E. arvense standardized for silicon and flavonoids andminerals.

These two examples indicate that the composition and method describedherein are effective in helping subjects control their symptoms ofUI/OAB and other bladder control problems without the side effects oftraditional medical treatments and provide effective prevention ortreatment of the symptoms of UI/OAB in a much shorter term than theprior herbal treatments.

Example 3 Case Studies Case 1

45 year old male with a history of bladder frequency since childhood. Hewas diagnosed as a child, via cystometric studies, as having a smallbladder. He was not medicated.

He presented urinary frequency, every 1.5 hours; nocturia (waking forthe toilet at night) every 1.5 to 2.5 hours.

If he consumed large quantities of alcohol (greater than 8 standarddrinks), he would experience flooding nocturesis (bed wetting). Inanticipation of nocturesis, he would lay down towels on bed whendrinking.

After 2 weeks on the herb-containing natural therapeutic bladder controlpreparation, he noticed improvement in day and night urinary frequency.Improvements in energy throughout the day were linked with reduction innight frequency. After 4 weeks, he was experiencing periods of up to 6.5hours in the day without the need for urination. Nocturia was an averageof 1 by this stage.

He then went on holiday for 2 weeks where daily drinking of alcohol wasinvolved. He expected the nocturesis to recur but found he had fullbladder control overnight over the entire 2 weeks.

After two months on the herb-containing natural therapeutic bladdercontrol preparation, his bladder control was in the ‘normal’classification of 6-8 times daily urination and maximum of one episodeof nocturia per night. He also had no nocturesis.

Case 2

73 year old woman with stress incontinence (2-7 times daily) and urinaryfrequency (11 times daily). She had previously tried Detrol and oraloxybutynin but could not tolerate the side effects of dry mouth andnasal passages. When presented, she was using oxybutynin patches(Oxytrol). A specialist recommended that she change patches every 3days. She found the drying side effects still occurred but to a lesserdegree, so the patches were more tolerable. The patches produced a rashfor her as well so she was actively seeking an alternative.

She stopped the oxybutynin patches (after the recommended 3 day period)and then commenced on the herb-containing natural therapeutic bladdercontrol preparation. Within two weeks, she was experiencing the sameeffects as the patches but without the side effects. The patient had nodiscernible side effects from the herb-containing natural therapeuticbladder control preparation. She has now been on the herb-containingnatural therapeutic bladder control preparation for 9 weeks, has had noincontinence episodes, and has normal urinary frequency.

Case 3

63 year old male presented with interstitial cystitis that had beenworsening for at least the past 5 years. He presented with penile pain(and some lower abdominal pain) that would increase in intensity thefuller his bladder, with relief on urination. As a result, he would needto urinate at least every 1.5 hours, day and night. If he went too long,the pain would increase to the point where he found it extremelydifficult to walk or move. Every month, he would have an episode,usually during the night, where he would pass copious amounts of bloodand some mucous from the bladder.

He would also find that every two weeks his symptom severity wouldincrease and he would have ‘horrific, sharp pain all day every day” fortwo days. He would urinate every half hour over these two days.

He is a farmer and whilst with frequent urination he could ‘manage’ hiscondition, he was finding it increasingly difficult, for example,especially if he was in the middle of an activity such as harvesting or‘under a truck doing repairs’. Also, he was extremely fatigued due towaking in pain and needing to empty his bladder every 1.5 hours.

He had been under the care of a urologist for two years. However, drugtherapy is not an option for him.

One year ago he had a bladder expansion procedure with good success. Hehad slight bleeding from the bladder post-operatively but had symptomrelief, which lasted about three months. He had another bladderexpansion procedure 6 months after the first and did not respond aswell. He had much greater blood loss post-operatively and his symptomsworsened significantly. It took three months for him to recover to thepoint he was at prior to the procedure. He is not willing to undergoanother bladder expansion procedure.

After three weeks on a double dose of the herb-containing naturaltherapeutic bladder control preparation (4 capsules daily), he felt anunusual sensation in the bladder and then for three or four days, whenurinating, he would pass predominantly blood and mucous.

After the fourth day, his urine returned back to normal and his daytimepenile pain did not reoccur. He was going to the toilet every 2.5 hours.Also, at night he could sleep for 2.5 hours before the pain would wakehim for the toilet.

He continued with the double dose of the herb-containing naturaltherapeutic bladder control preparation and at the 2.5 month stage hisoverall pain is “minimal” and he can go up to 4 hours without having toget up at night for the toilet.

The pain does still recur twice weekly for half a day where he needs tourinate every hour (previously this would occur every two weeks and hewould need to urinate every half hour for 2 days). He did have a slightbleed from the bladder in the middle of the night at the month 2 stage.Otherwise there has been no blood loss from the bladder since threeweeks of treatment.

If all is progressing well, at 3 months his dose will be reduced to 2capsules daily.

Equivalents

This invention has been described in terms of specific embodiments setforth in detail herein, but it should be understood that these are byway of illustration and the invention is not necessarily limitedthereto. Modifications and variations will be apparent from thedisclosure and may be resorted to without departing from the spirit ofthe invention as those of skill in the art will readily understand.Accordingly, such variations and modifications are considered to bewithin the purview and scope of the invention and the following claims.

What is claimed:
 1. An herb-containing composition, comprising: (i) aCrateva nurvala extract preparation; (ii) an Equisetum arvense extractpreparation; and (iii) a Lindera aggregata extract preparation; whereinthe herb-containing composition is formulated as an oral dosage unit. 2.The herb-containing composition of claim 1, wherein the Crateva nurvalapreparation is present at a concentration from about 1 g to about 18 gdry weight equivalents per oral dosage unit.
 3. The herb-containingcomposition of claim 1, wherein the Equisetum arvense extractpreparation is present at a concentration from about 750 mg to about 12g dry weight equivalents per oral dosage unit.
 4. The herb-containingcomposition of claim 1, wherein the Lindera aggregata extractpreparation is present at a concentration from about 750 mg to about 12g dry weight equivalents per oral dosage unit.
 5. The herb-containingcomposition of claim 1, wherein the Crateva nurvala preparation ispresent at a concentration from about 3 g to about 12 g dry weightequivalents per oral dosage unit.
 6. The herb-containing composition ofclaim 1, wherein the Equisetum arvense extract preparation is present ata concentration from about 1.5 g to about 6 g dry weight equivalents peroral dosage unit.
 7. The herb-containing composition of claim 1, whereinthe Lindera aggregata extract preparation is present at a concentrationfrom about 1.5 g to about 6 g dry weight equivalents per oral dosageunit.
 8. The herb-containing composition of claim 1, wherein the Cratevanurvala preparation is present at a concentration from about 4 g toabout 8 g dry weight equivalents per oral dosage unit.
 9. Theherb-containing composition of claim 1, wherein the Equisetum arvenseextract preparation is present at a concentration from about 2 g toabout 4 g dry weight equivalents per oral dosage unit.
 10. Theherb-containing composition of claim 1, wherein the Lindera aggregataextract preparation is present at a concentration from about 2 g toabout 4 g dry weight equivalents per oral dosage unit.
 11. Theherb-containing composition of claim 1, wherein the composition has atleast one of the following: (i) the Crateva nurvala extract preparationis a stem/bark extract preparation; (ii) the Equisetum arvense extractpreparation is a stem extract preparation; and (iii) the Linderaaggregata extract preparation is a root extract preparation.
 12. Theherb-containing composition of claim 1, wherein the herb-containingcomposition is formulated in a dry delivery system.
 13. Theherb-containing composition of claim 1, wherein the herb-containingcomposition is formulated in a liquid delivery system.
 14. Theherb-containing composition of claim 1, wherein the herb-containingcomposition is formulated in a controlled-release vehicle.
 15. Apharmaceutical composition comprising the herb-containing composition ofclaim 1 and a pharmaceutically-acceptable carrier.
 16. Anherb-containing composition, comprising: (i) a Crateva nurvala stem/barkextract preparation present; (ii) an Equisetum arvense stem extractpreparation; (iii) a Lindera aggregata root extract preparation; whereinthe herb-containing composition is formulated as an oral dosage unit,and wherein the Equisetum arvense stem extract preparation and theLindera aggregata root extract preparation are present at the sameconcentration.
 17. The herb-containing composition of claim 16, whereinthe Crateva nurvala stem/bark preparation is present at a concentrationof at least about 3,000 mg dry weight equivalents per oral dosage unit.18. The herb-containing composition of claim 16, wherein the Equisetumarvense stem extract preparation is present at a concentration of atleast about 1,500 mg dry weight equivalents per oral dosage unit. 19.The herb-containing composition of claim 16, wherein the Linderaaggregata root extract preparation is present at a concentration of atleast about 1,500 mg dry weight equivalents per oral dosage unit.
 20. Apharmaceutical composition comprising the herb-containing composition ofclaim 16 and a pharmaceutically-acceptable carrier.
 21. Theherb-containing composition of claim 1, wherein the oral dosage unit isselected from the group consisting of: a tablet, dry powder, capsule,and caplet.
 22. A method for the prevention or treatment of the symptomsof urinary incontinence or overactive bladder, comprising: administeringan herb-containing composition to a subject in need thereof, theherb-containing composition comprising: (i) a Crateva nurvala extractpreparation; (ii) an Equisetum arvense extract preparation; and (iii) aLindera aggregata extract preparation; wherein the herb-containingcomposition is formulated as an oral dosage unit.
 23. The method ofclaim 22, wherein the treatment results in a reduction in at least oneof (i) urinary incontinence and (ii) overactive bladder symptom afterabout two weeks.
 24. The method of claim 22, wherein the treatmentresults in a reduction in at least one of (i) urinary incontinence and(ii) overactive bladder symptom after about one month.
 25. The method ofclaim 22, wherein, compared to a subject not administered theherb-containing composition, the treatment results in an improvement ofat least one of: (i) average daily frequency of urination; (ii) averagenightly frequency of urination; (iii) total urinary incontinenceepisodes; (iv) stress incontinence episodes; and (v) urinary urgencyepisodes.
 26. The method of claim 22, further comprising at least one ofthe following: (i) extracting the Crateva nurvala preparation fromCrateva nurvala stem/bark at an extract ratio of between about 25 and35; (ii) extracting the Equisetum arvense extract preparation fromEquisetum arvense stem at an extract ratio of about 10; and (iii)extracting the Lindera aggregata preparation from Lindera aggregata rootat an extract ratio of about 10.